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Applications and Health
NIR-II-Responsive Versatile Nanozyme Based on H2O2 Cycling and Disrupting Cellular Redox Homeostasis for Enhanced Synergistic Cancer Therapy
基于 H2O2 循环和破坏细胞氧化还原稳态的 NIR-II 响应性多功能纳米酶，用于增强协同癌症治疗Click to copy article linkArticle link copied!
- Pinghua ling*Pinghua ling*Email: phling@ahnu.edu.cnLaboratory of Functionalized Molecular Solids, Ministry of Education, Anhui Province Key Laboratory of Biomedical Materials and Chemical Measurement, College of Chemistry and Materials Science, Anhui Normal University, Wuhu 241002, ChinaMore by Pinghua ling
- Danjie SongDanjie SongLaboratory of Functionalized Molecular Solids, Ministry of Education, Anhui Province Key Laboratory of Biomedical Materials and Chemical Measurement, College of Chemistry and Materials Science, Anhui Normal University, Wuhu 241002, ChinaMore by Danjie Song
- Pei YangPei YangLaboratory of Functionalized Molecular Solids, Ministry of Education, Anhui Province Key Laboratory of Biomedical Materials and Chemical Measurement, College of Chemistry and Materials Science, Anhui Normal University, Wuhu 241002, ChinaMore by Pei Yang
- Chuanye TangChuanye TangLaboratory of Functionalized Molecular Solids, Ministry of Education, Anhui Province Key Laboratory of Biomedical Materials and Chemical Measurement, College of Chemistry and Materials Science, Anhui Normal University, Wuhu 241002, ChinaMore by Chuanye Tang
- Wenwen XuWenwen XuLaboratory of Functionalized Molecular Solids, Ministry of Education, Anhui Province Key Laboratory of Biomedical Materials and Chemical Measurement, College of Chemistry and Materials Science, Anhui Normal University, Wuhu 241002, ChinaMore by Wenwen Xu
- Fang Wang*Fang Wang*Email: wangfang900816@163.comInstitute of Clinical Pharmacy, Jining No. 1 People’s Hospital, Shandong First Medical University, Jining 272000, Shandong, ChinaMore by Fang Wang
Abstract
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Disturbing cellular redox homeostasis within malignant cells, particularly improving reactive oxygen species (ROS), is one of the effective strategies for cancer therapy. The ROS generation based on nanozymes presents a promising strategy for cancer treatment. However, the therapeutic efficacy is limited due to the insufficient catalytic activity of nanozymes or their high dependence on hydrogen peroxide (H2O2) or oxygen. Herein, we reported a nanozyme (CSA) based on well-defined CuSe hollow nanocubes (CS) uniformly covered with Ag nanoparticles (AgNPs) to disturb cellular redox homeostasis and catalyze a cascade of intracellular biochemical reactions to produce ROS for the synergistic therapy of breast cancer. In this system, CSA could interact with the thioredoxin reductase (TrxR) and deplete the tumor microenvironment-activated glutathione (GSH), disrupting the cellular antioxidant defense system and augmenting ROS generation. Besides, CSA possessed high peroxidase-mimicking activity toward H2O2, leading to the generation of various ROS including hydroxyl radical (•OH), superoxide radicals (•O2–), and singlet oxygen (1O2), facilitated by the Cu(II)/Cu(I) redox and H2O2 cycling, and plentiful catalytically active metal sites. Additionally, due to the absorption and charge separation performance of AgNPs, the CSA exhibited excellent photothermal performance in the second near-infrared (NIR-II, 1064 nm) region and enhanced the photocatalytic ROS level in cancer cells. Owing to the inhibition of TrxR activity, GSH depletion, high peroxidase-mimicking activity of CSA, and abundant ROS generation, CSA displays remarkable and specific inhibition of tumor growth.
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1. Introduction 1. 引言
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Reactive oxygen species (ROS), encompassing highly reactive ions and free radicals such as singlet oxygen (1O2), superoxide radicals (•O2–), hydroxyl radicals (•OH), and peroxides (O22–), play pivotal roles in various physiological processes. (1,2) As the key mediators of cellular oxidative stress, ROS at the normal concentration are indispensable for the development of living organisms, such as cellular signaling, homeostasis, and metabolism. Conversely, an overproduction of ROS is associated with cellular pathological states including cancer, neurodegenerative diseases, and inflammation. (3−6) Elevated ROS levels could induce cellular oxidative stress, leading to lipids, proteins, and DNA damage, culminating in cell apoptosis. As a result, numerous approaches based on leveraging excessive ROS at pathological sites have been developed for cancer therapy, such as photodynamic therapy, (7) sonodynamic therapy, (8,9) radiation therapy, (10) chemodynamic therapy, (11) and synergistic therapy. (12,13) However, the limited concentration of H2O2, the overexpression of glutathione (GSH) and hypoxic environment in cancer cells, the relatively low tissue-penetrating depth of the laser, and the relatively low activity of the probe still hampered the treatment effect. Therefore, there is an urgent need to design a strategy that could disturb the redox homeostasis and overcome the tumor microenvironment to enhance ROS generation for improved cancer therapy.
活性氧 （ROS） 包括高反应性离子和自由基，如单线态氧 （1O2）、超氧自由基 （•O2–）、羟基自由基 （•OH） 和过氧化物 （O22–），在各种生理过程中起着关键作用。（1,2） 作为细胞氧化应激的关键介质，正常浓度的 ROS 对于生物体的发育是必不可少的，例如细胞信号传导、稳态和新陈代谢。相反，ROS 的过量产生与细胞病理状态有关，包括癌症、神经退行性疾病和炎症。（3-6） ROS 水平升高可诱导细胞氧化应激，导致脂质、蛋白质和 DNA 损伤，最终导致细胞凋亡。因此，已经开发了许多基于在病理部位利用过量 ROS 的方法进行癌症治疗，例如光动力疗法，（7） 声动力疗法，（8,9） 放射疗法，（10） 化学动力学疗法，（11） 和协同疗法。（12,13） 然而，H2O2 的浓度有限、谷胱甘肽 （GSH） 的过表达和癌细胞中的低氧环境、激光相对较低的组织穿透深度以及探针的相对较低的活性仍然阻碍了治疗效果。因此，迫切需要设计一种策略，可以扰乱氧化还原稳态并克服肿瘤微环境，以增强 ROS 的产生以改善癌症治疗。
活性氧 （ROS） 包括高反应性离子和自由基，如单线态氧 （1O2）、超氧自由基 （•O2–）、羟基自由基 （•OH） 和过氧化物 （O22–），在各种生理过程中起着关键作用。（1,2） 作为细胞氧化应激的关键介质，正常浓度的 ROS 对于生物体的发育是必不可少的，例如细胞信号传导、稳态和新陈代谢。相反，ROS 的过量产生与细胞病理状态有关，包括癌症、神经退行性疾病和炎症。（3-6） ROS 水平升高可诱导细胞氧化应激，导致脂质、蛋白质和 DNA 损伤，最终导致细胞凋亡。因此，已经开发了许多基于在病理部位利用过量 ROS 的方法进行癌症治疗，例如光动力疗法，（7） 声动力疗法，（8,9） 放射疗法，（10） 化学动力学疗法，（11） 和协同疗法。（12,13） 然而，H2O2 的浓度有限、谷胱甘肽 （GSH） 的过表达和癌细胞中的低氧环境、激光相对较低的组织穿透深度以及探针的相对较低的活性仍然阻碍了治疗效果。因此，迫切需要设计一种策略，可以扰乱氧化还原稳态并克服肿瘤微环境，以增强 ROS 的产生以改善癌症治疗。
The thioredoxin (Trx) system, particularly thioredoxin reductase (TrxR), plays crucial roles in the regulation of intracellular redox homeostasis and has been identified as a novel target for anticancer drug owing to its overexpression in various aggressive tumors. (14) TrxR, which is a selenoprotein, could reduce the oxidoreductase Trx in a NADPH-dependent manner, thereby maintaining the intracellular redox balance. Inhibition of TrxR could disrupt the cellular antioxidant defense system, leading to an increase in ROS generation. (15,16) Thus, the inhibition of TrxR activity may represent a potential strategy for cancer therapy.
硫氧还蛋白 （Trx） 系统，特别是硫氧还蛋白还原酶 （TrxR），在细胞内氧化还原稳态的调节中起着至关重要的作用，并且由于其在各种侵袭性肿瘤中的过表达而被确定为抗癌药物的新靶点。（14） TrxR 是一种硒蛋白，可以以 NADPH 依赖性方式还原氧化还原酶 Trx，从而维持细胞内氧化还原平衡。抑制 TrxR 会破坏细胞抗氧化防御系统，导致 ROS 生成增加。（15,16） 因此，抑制 TrxR 活性可能代表了癌症治疗的潜在策略。
硫氧还蛋白 （Trx） 系统，特别是硫氧还蛋白还原酶 （TrxR），在细胞内氧化还原稳态的调节中起着至关重要的作用，并且由于其在各种侵袭性肿瘤中的过表达而被确定为抗癌药物的新靶点。（14） TrxR 是一种硒蛋白，可以以 NADPH 依赖性方式还原氧化还原酶 Trx，从而维持细胞内氧化还原平衡。抑制 TrxR 会破坏细胞抗氧化防御系统，导致 ROS 生成增加。（15,16） 因此，抑制 TrxR 活性可能代表了癌症治疗的潜在策略。
Nanozymes, synthetic materials possessing one or more enzyme mimicking activity, (17−20) have garnered considerable attention in recent years. Due to their controlled synthesis, high stability, and tunable catalytic activities, nanozymes have been extensively employed in a variety of applications, biosensing, cancer therapy, imaging, and so on. (21−25) Recently, a wide array of nanozymes, such as metal oxides, (26−28) metal nanoparticles, (29) carbon nanomaterials, (30,31) and their composites, (24) have been utilized for the treatment of various diseases based on their enzyme-like activities. However, the insufficient catalytic efficiency within the tumor microenvironment remains a considerable challenge.
纳米酶是具有一种或多种酶模拟活性 （17−20） 的合成材料，近年来引起了相当大的关注。由于其可控的合成、高稳定性和可调的催化活性，纳米酶已被广泛用于各种应用，如生物传感、癌症治疗、成像等。（21−25） 最近，各种纳米酶，如金属氧化物、（26−28） 金属纳米颗粒、（29） 碳纳米材料、（30,31） 及其复合材料 （24） 已根据其酶样活性被用于治疗各种疾病。然而，肿瘤微环境中的催化效率不足仍然是一个相当大的挑战。
纳米酶是具有一种或多种酶模拟活性 （17−20） 的合成材料，近年来引起了相当大的关注。由于其可控的合成、高稳定性和可调的催化活性，纳米酶已被广泛用于各种应用，如生物传感、癌症治疗、成像等。（21−25） 最近，各种纳米酶，如金属氧化物、（26−28） 金属纳米颗粒、（29） 碳纳米材料、（30,31） 及其复合材料 （24） 已根据其酶样活性被用于治疗各种疾病。然而，肿瘤微环境中的催化效率不足仍然是一个相当大的挑战。
In order to enhance the catalytic activity of nanozymes, various modulation strategies have been used, including optical, acoustic, and new reagents. Among these methods, light, specifically near-infrared II light (NIR II, 1000–1350 nm), provides numerous advantages such as lower tissue background, superior temporal, and spatial resolution. (32−34) Under NIR II, nanozymes could generate enhanced ROS due to the direct electron transfer, light-enhanced catalytic reactions, and photothermal effect. (35,36) In order to extend the light absorption range of the nanozymes, some metal nanoparticles, such as silver nanoparticles (AgNPs), and gold nanoparticles have been utilized for nanozyme modification. Due to the surface plasmon resonance (SPR) effects of metal nanoparticles, the metal nanoparticle-decorated nanozymes demonstrate a widened absorption band in the visible light spectrum, thereby improving visible light utilization and photocatalytic activity. (37−39) Therefore, the design of nanozymes with high catalytic activity and NIR II absorption holds promise for enhanced cancer therapy.
为了增强纳米酶的催化活性，已经使用了各种调制策略，包括光学、声学和新试剂。在这些方法中，光，特别是近红外 II 光 （NIR II， 1000–1350 nm） 具有许多优势，例如较低的组织背景、卓越的时间和空间分辨率。（32−34） 在 NIR II 下，由于直接电子转移、光增强催化反应和光热效应，纳米酶可以产生增强的 ROS。（35,36） 为了扩大纳米酶的光吸收范围，一些金属纳米颗粒，如银纳米颗粒 （AgNPs） 和金纳米颗粒已被用于纳米酶修饰。由于金属纳米粒子的表面等离子体共振 （SPR） 效应，金属纳米粒子修饰的纳米酶在可见光谱中表现出加宽的吸收带，从而提高了可见光利用率和光催化活性。（37−39） 因此，具有高催化活性和 NIR II 吸收的纳米酶的设计有望增强癌症治疗。
为了增强纳米酶的催化活性，已经使用了各种调制策略，包括光学、声学和新试剂。在这些方法中，光，特别是近红外 II 光 （NIR II， 1000–1350 nm） 具有许多优势，例如较低的组织背景、卓越的时间和空间分辨率。（32−34） 在 NIR II 下，由于直接电子转移、光增强催化反应和光热效应，纳米酶可以产生增强的 ROS。（35,36） 为了扩大纳米酶的光吸收范围，一些金属纳米颗粒，如银纳米颗粒 （AgNPs） 和金纳米颗粒已被用于纳米酶修饰。由于金属纳米粒子的表面等离子体共振 （SPR） 效应，金属纳米粒子修饰的纳米酶在可见光谱中表现出加宽的吸收带，从而提高了可见光利用率和光催化活性。（37−39） 因此，具有高催化活性和 NIR II 吸收的纳米酶的设计有望增强癌症治疗。
Lung cancer is one of the most common malignant tumors with the highest incidence in the world. The high mortality rate of lung cancer is mainly due to drug resistance and the immunosuppression, which limits the effectiveness of anticancer drugs and induces tumor cell resistance. In this work, lung cancer was selected as a model. We fabricated a multifunctional nanozyme (CSA) based on Ag-doped hollow CuSe (CS) with disturbing cellular redox homeostasis, high catalytic activity, and NIR II absorbance for synergistic lung cancer therapy (Scheme 1). The CS nanozyme with a hollow structure was prepared by using Cu2O nanocubes as templates and Na2SeO3 as a selenium source via anion exchange, followed by in situ growth of AgNPs to construct the CSA nanozyme. In this system, CSA displayed remarkable peroxidase-mimicking activity, enabling it to interact with H2O2 to generate a variety of ROS including •OH, •O2–, and 1O2, which can be attributed to the rapid redox cycling of Cu(II)/Cu(I) redox and H2O2, and abundant catalytically active metal binding sites. Upon 1064 nm laser irradiation, CSA demonstrated high photocatalytic activity due to the ability of AgNPs to capture electrons from the CS via the metal to metal charge transfer, thereby reducing O2 to generate •O2–, and leading to an increase in ROS generation. Moreover, Cu and Se in CSA could deplete GSH, disrupting the cellular antioxidant defense system and resulting in more ROS release. In addition, thioredoxin reductase which is an important selenocysteine (Sec)-containing antioxidant enzyme, plays a pivotal role in regulating intracellular redox balance. (40,41) Due to the presence of Se and AgNPs, CSA could react with the Sec residue in TrxR to inhibit its oxidoreductase thioredoxin reduction activity, leading to a novel pathway for generating ROS. (15,42) Therefore, the synergistic combination of high catalytic activity, NIR II absorbance, GSH depletion, and TrxR inhibition of CSA significantly enhances ROS generation and tumor therapy efficacy. Hence, this work will offer valuable insights into the design of a novel nanozyme for multifunctional synergistic antitumor therapy.
肺癌是世界上发病率最高的最常见恶性肿瘤之一。肺癌的高死亡率主要是由于耐药性和免疫抑制作用，限制了抗癌药物的有效性，诱导了肿瘤细胞耐药。在这项工作中，肺癌被选为模型。我们制造了一种基于 Ag 掺杂空心 CuSe （CS） 的多功能纳米酶 （CSA），具有令人不安的细胞氧化还原稳态、高催化活性和 NIR II 吸光度，用于协同肺癌治疗（方案 1）。以 Cu2O 纳米立方体为模板，Na2SeO3 为硒源，通过阴离子交换制备具有中空结构的 CS 纳米酶，然后原位生长 AgNPs 构建 CSA 纳米酶。在该系统中，CSA 表现出显着的过氧化物酶模拟活性，使其能够与 H2O2 相互作用以产生多种 ROS，包括 •OH、•O2– 和 1O2，这可归因于 Cu（II）/Cu（I） 氧化还原和 H2O2 的快速氧化还原循环，以及丰富的催化活性金属结合位点。在 1064 nm 激光照射下，由于 AgNP 能够通过金属到金属的电荷转移从 CS 捕获电子，从而减少 O2 生成 •O2–，并导致 ROS 生成增加，因此 CSA 表现出高光催化活性。此外，CSA 中的 Cu 和 Se 会消耗 GSH，破坏细胞抗氧化防御系统并导致更多的 ROS 释放。 此外，硫氧还蛋白还原酶是一种重要的含硒代半胱氨酸 （Sec） 的抗氧化酶，在调节细胞内氧化还原平衡中起着关键作用。（40,41） 由于 Se 和 AgNPs 的存在，CSA 可以与 TrxR 中的 Sec 残基反应以抑制其氧化还原酶硫氧还蛋白还原活性，从而产生 ROS 的新途径。（15,42） 因此，CSA 的高催化活性、NIR II 吸光度、GSH 耗竭和 TrxR 抑制的协同组合显着增强了 ROS 的产生和肿瘤治疗效果。因此，这项工作将为设计用于多功能协同抗肿瘤治疗的新型纳米酶的设计提供有价值的见解。
肺癌是世界上发病率最高的最常见恶性肿瘤之一。肺癌的高死亡率主要是由于耐药性和免疫抑制作用，限制了抗癌药物的有效性，诱导了肿瘤细胞耐药。在这项工作中，肺癌被选为模型。我们制造了一种基于 Ag 掺杂空心 CuSe （CS） 的多功能纳米酶 （CSA），具有令人不安的细胞氧化还原稳态、高催化活性和 NIR II 吸光度，用于协同肺癌治疗（方案 1）。以 Cu2O 纳米立方体为模板，Na2SeO3 为硒源，通过阴离子交换制备具有中空结构的 CS 纳米酶，然后原位生长 AgNPs 构建 CSA 纳米酶。在该系统中，CSA 表现出显着的过氧化物酶模拟活性，使其能够与 H2O2 相互作用以产生多种 ROS，包括 •OH、•O2– 和 1O2，这可归因于 Cu（II）/Cu（I） 氧化还原和 H2O2 的快速氧化还原循环，以及丰富的催化活性金属结合位点。在 1064 nm 激光照射下，由于 AgNP 能够通过金属到金属的电荷转移从 CS 捕获电子，从而减少 O2 生成 •O2–，并导致 ROS 生成增加，因此 CSA 表现出高光催化活性。此外，CSA 中的 Cu 和 Se 会消耗 GSH，破坏细胞抗氧化防御系统并导致更多的 ROS 释放。 此外，硫氧还蛋白还原酶是一种重要的含硒代半胱氨酸 （Sec） 的抗氧化酶，在调节细胞内氧化还原平衡中起着关键作用。（40,41） 由于 Se 和 AgNPs 的存在，CSA 可以与 TrxR 中的 Sec 残基反应以抑制其氧化还原酶硫氧还蛋白还原活性，从而产生 ROS 的新途径。（15,42） 因此，CSA 的高催化活性、NIR II 吸光度、GSH 耗竭和 TrxR 抑制的协同组合显着增强了 ROS 的产生和肿瘤治疗效果。因此，这项工作将为设计用于多功能协同抗肿瘤治疗的新型纳米酶的设计提供有价值的见解。
Scheme 1 方案 1
Scheme 1. Illustration of (A) Synthetic Process of CSA and (B) Proposed Antitumor Mechanism of CSA for Improved Photothermal Therapy
方案 1.（a） CSA 的合成过程和 （b） 提出的 CSA 抗肿瘤机制用于改进光热疗法的插图
方案 1.（a） CSA 的合成过程和 （b） 提出的 CSA 抗肿瘤机制用于改进光热疗法的插图
2. Results and Discussion
2. 结果与讨论
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2.1. Synthesis and Characterization of CSA
2.1. CSA 的综合和表征
Hollow CuSe (CS) was prepared by using Cu2O nanospheres as templates and Na2SeO3 as a selenium source via anion exchange based on the Kirkendall effect. (43) Initially, ascorbic acid and a solution of Cu2+ and NaOH were employed to synthesize Cu2O. It can be seen from Figure 1A that the synthesized Cu2O exhibited a regular cubic morphology with a diameter ranging from 80 to 90 nm. In order to further reveal the structure of Cu2O, high-resolution TEM (HR-TEM) and elemental mapping images were performed. The HR-TEM image displayed the presence of Cu and O elements within Cu2O, with a lattice spacing of approximately 0.245 nm. The spacing is increased with the (222) crystal planes of the cubic Cu2O crystal (Figure S1A). When Cu2O was reacted with Se2– solution via ion-exchanging, the formed CuSe (CS) was measured by TEM and HR-TEM. As shown in Figure 1B, the synthesized CS nanoparticles displayed a hollow cubic structure with diameters of approximately 80–90 nm. The HR-TEM revealed that Cu and Se elements were observed in CS, and the lattice spacing of CS was ∼0.326 nm, which was in good agreement with the (101) crystal planes of CS (Figure S1B). The addition of silver nitrate (AgNO3) to CS led to the formation of AgNPs on the surface of the CS. Figure 1C confirms the presence of AgNPs, with a size of approximately 10 nm, within the CuSe@Ag (CSA) nanocomposites. A distinct set of visible lattice fringes, with a spacing of 0.234 nm, was observed in the HR-TEM image of the CSA nanocomposites, which corresponds to the (111) plane spacing of Ag (Figure 1D). (44) Elemental mapping images of CSA confirmed the presence of Cu, Se, and Ag in CSA, indicating the successful formation of AgNPs on the surface of CS (Figure 1E). In addition, energy-dispersive spectroscopy and elemental mapping of the CSA implied the presence of Se, Ag, and Cu elements within the synthesized CSA (Figures S2 and S3). These results suggested that the CSA was successfully synthesized. In Fourier transform infrared spectra (FTIR) (Figure S4), the peak at 633 cm–1 corresponded to the Cu–O stretching vibration in the Cu2O phase. (45) The peak at 863 cm–1 indicated the presence of CuSe. (46) The 633 cm–1 peak diminished and the 430 cm–1 peak increased, suggesting the AgNPs formed. (45,47) FTIR also confirmed the formation of CSA.
以 Cu2O 纳米球为模板，Na2SeO3 为硒源，基于 Kirkendall 效应，通过阴离子交换制备空心 CuSe （CS）。（43） 最初，使用抗坏血酸和 Cu2+ 和 NaOH 的溶液合成 Cu2O。从图 1A 中可以看出，合成的 Cu2O 表现出直径为 80 至 90 nm 的规则立方形貌。为了进一步揭示 Cu2O 的结构，进行了高分辨率 TEM （HR-TEM） 和元素映射图像。HR-TEM 图像显示 Cu2O 中存在 Cu 和 O 元素，晶格间距约为 0.245 nm。间距随着立方 Cu2O 晶体的 （222） 晶面的增加而增加（图 S1A）。当 Cu2O 通过离子交换与 Se2– 溶液反应时，通过 TEM 和 HR-TEM 测量形成的 CuSe （CS）。如图 1B 所示，合成的 CS 纳米颗粒显示出直径约为 80-90 nm 的空心立方结构。HR-TEM 显示，在 CS 中观察到 Cu 和 Se 元素，CS 的晶格间距为 ∼0.326 nm，与 CS 的 （101） 晶面非常吻合（图 S1B）。向 CS 中添加硝酸银 （AgNO3） 导致在 CS 表面形成 AgNP。图 1C 证实了 CuSe@Ag （CSA） 纳米复合材料中存在大小约为 10 nm 的 AgNP。在 CSA 纳米复合材料的 HR-TEM 图像中观察到一组间距为 0.234 nm 的可见晶格条纹，这与 Ag 的 （111） 平面间距相对应（图 1D）。 （44） CSA 的元素映射图像证实了 CSA 中存在 Cu、Se 和 Ag，表明 AgNPs 在 CS 表面成功形成（图 1E）。此外，CSA 的能量色散光谱和元素映射表明合成的 CSA 中存在 Se、Ag 和 Cu 元素（图 S2 和 S3）。这些结果表明 CSA 合成成功。在傅里叶变换红外光谱 （FTIR） 中（图 S4），633 cm–1 处的峰对应于 Cu2O 相中的 Cu-O 拉伸振动。（45） 863 cm–1 处的峰表明存在 CuSe。（46） 633 cm-1 峰减小，430 cm-1 峰增加，表明 AgNPs 形成。（45,47） FTIR 也证实了 CSA 的形成。
以 Cu2O 纳米球为模板，Na2SeO3 为硒源，基于 Kirkendall 效应，通过阴离子交换制备空心 CuSe （CS）。（43） 最初，使用抗坏血酸和 Cu2+ 和 NaOH 的溶液合成 Cu2O。从图 1A 中可以看出，合成的 Cu2O 表现出直径为 80 至 90 nm 的规则立方形貌。为了进一步揭示 Cu2O 的结构，进行了高分辨率 TEM （HR-TEM） 和元素映射图像。HR-TEM 图像显示 Cu2O 中存在 Cu 和 O 元素，晶格间距约为 0.245 nm。间距随着立方 Cu2O 晶体的 （222） 晶面的增加而增加（图 S1A）。当 Cu2O 通过离子交换与 Se2– 溶液反应时，通过 TEM 和 HR-TEM 测量形成的 CuSe （CS）。如图 1B 所示，合成的 CS 纳米颗粒显示出直径约为 80-90 nm 的空心立方结构。HR-TEM 显示，在 CS 中观察到 Cu 和 Se 元素，CS 的晶格间距为 ∼0.326 nm，与 CS 的 （101） 晶面非常吻合（图 S1B）。向 CS 中添加硝酸银 （AgNO3） 导致在 CS 表面形成 AgNP。图 1C 证实了 CuSe@Ag （CSA） 纳米复合材料中存在大小约为 10 nm 的 AgNP。在 CSA 纳米复合材料的 HR-TEM 图像中观察到一组间距为 0.234 nm 的可见晶格条纹，这与 Ag 的 （111） 平面间距相对应（图 1D）。 （44） CSA 的元素映射图像证实了 CSA 中存在 Cu、Se 和 Ag，表明 AgNPs 在 CS 表面成功形成（图 1E）。此外，CSA 的能量色散光谱和元素映射表明合成的 CSA 中存在 Se、Ag 和 Cu 元素（图 S2 和 S3）。这些结果表明 CSA 合成成功。在傅里叶变换红外光谱 （FTIR） 中（图 S4），633 cm–1 处的峰对应于 Cu2O 相中的 Cu-O 拉伸振动。（45） 863 cm–1 处的峰表明存在 CuSe。（46） 633 cm-1 峰减小，430 cm-1 峰增加，表明 AgNPs 形成。（45,47） FTIR 也证实了 CSA 的形成。
Figure 1 图 1
Figure 1. TEM images of (A) Cu2O NPs, (B) CS NPs, and (C) CSA NPs. (D) HR-TEM image of CSA. (E) HAADF-STEM image and elemental mappings of Cu, Se, and Ag elements in CSA NPs. (F) XRD spectra for Cu2O NPs, CS NPs, and CSA NPs. (G) Full XPS spectra for CS and CSA. High-resolution XPS spectra for (H) Cu 2p, (I) Se 3d, and (J) Ag 3d in CSA.
图 1.（A） Cu2O NPs、（B） CS NPs 和 （C） CSA NPs 的 TEM 图像。（D） CSA 的 HR-TEM 图像。（E） CSA NPs中Cu、Se和Ag元素的HAADF-STEM图像和元素映射。（F） Cu2O NPs、CS NPs和CSA NPs的XRD光谱。（G） CS和CSA的完整XPS光谱。CSA 中 （H） Cu 2p、（I） Se 3d 和 （J） Ag 3d 的高分辨率 XPS 光谱。
In order to further elucidate the structure of the as-prepared CSA, X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) were conducted. As depicted in Figure 1F, the peaks at 29.5, 36.2, 42.6, 61.7, and 73.9° were indexed to the (110), (111), (200), (220), and (311) crystal planes of Cu2O, respectively (JCPDS #65-3288). Additionally, the peaks at 27.5, 43.6, and 52.7° corresponded to the (110), (220), (200), and (311) crystal planes of CS, respectively (JCPDS #86-1240). The peak at 38.1° was observed in the CSA, which could be indexed to the (111) crystal planes of Ag. The XPS spectrum of CSA is shown in Figure 1G. It can be seen that Cu 2p, Ag 3d, and Se 3d elemental signals were observed in the XPS spectrum of CSA. In the Cu 2p spectra (Figure 1H), the peaks at 931.7 and 951.2 eV were assigned to Cu+ or Cu0, and the peaks at 933.92 and 954.62 eV were assigned to Cu2+, (22,23,48) implying a mixed valence state of copper elements in the synthesized CSA nanoparticles. For the high-resolution XPS of Se 3d (Figure 1I), the peaks at 53.8 and 53.3 eV corresponded to Se 3d3/2 and Se 3d5/2, respectively, and the peak at 57.8 eV is due to SeOx. (49−51) In the Ag 3d spectrum (Figure 1J), the appearance of the peaks at 368.5 and 374.5 eV was indexed to Ag 3d5/2 and Ag 3d3/2, respectively, demonstrating that the valence state of Ag was zero and the formation of pure metallic Ag on the surface of CS. (52,53) These results indicated that the as-prepared CSA possesses desirable characteristics for biomedical applications. Additionally, the presence of both Cu(I) and Cu(II) in the CSA could be favorable for achieving mimicking activity under weakly acidic conditions.
为了进一步阐明所制备的 CSA 的结构，进行了 X 射线衍射 （XRD） 和 X 射线光电子能谱 （XPS）。如图 1F 所示，29.5、36.2、42.6、61.7 和 73.9° 处的峰分别标入 Cu2O 的 （110）、（111）、（200）、（220） 和 （311） 晶面 （JCPDS #65-3288）。此外，27.5°、43.6°和52.7°处的峰分别对应于CS的（110）、（220）、（200）和（311）晶面（JCPDS #86-1240）。在 CSA 中观察到 38.1° 的峰，该峰可以索引到 Ag 的 （111） 晶面。CSA 的 XPS 光谱如图 1G 所示。可以看出，在 CSA 的 XPS 谱中观察到 Cu 2p、Ag 3d 和 Se 3d 元素信号。在 Cu 2p 光谱中（图 1H），931.7 和 951.2 eV 处的峰被分配给 Cu+ 或 Cu 0,933.92 和 954.62 eV 处的峰被分配给 Cu2+，（22,23,48），这意味着合成的 CSA 纳米颗粒中铜元素的价态混合。对于 Se 3d 的高分辨率 XPS（图 1I），53.8 和 53.3 eV 处的峰分别对应于 Se 3d3/2 和 Se 3d5/2,57.8 eV 处的峰是由于 SeOx 引起的。（49−51） 在 Ag 3d 光谱（图 1J）中，368.5 和 374.5 eV 处峰的出现分别标于 Ag 3d5/2 和 Ag 3d3/2，表明 Ag 的价态为零，并且在 CS 表面形成纯金属 Ag。（52,53） 这些结果表明，制备的 CSA 具有生物医学应用的理想特性。 此外，CSA 中 Cu（I） 和 Cu（II） 的存在可能有利于在弱酸性条件下实现模拟活性。
为了进一步阐明所制备的 CSA 的结构，进行了 X 射线衍射 （XRD） 和 X 射线光电子能谱 （XPS）。如图 1F 所示，29.5、36.2、42.6、61.7 和 73.9° 处的峰分别标入 Cu2O 的 （110）、（111）、（200）、（220） 和 （311） 晶面 （JCPDS #65-3288）。此外，27.5°、43.6°和52.7°处的峰分别对应于CS的（110）、（220）、（200）和（311）晶面（JCPDS #86-1240）。在 CSA 中观察到 38.1° 的峰，该峰可以索引到 Ag 的 （111） 晶面。CSA 的 XPS 光谱如图 1G 所示。可以看出，在 CSA 的 XPS 谱中观察到 Cu 2p、Ag 3d 和 Se 3d 元素信号。在 Cu 2p 光谱中（图 1H），931.7 和 951.2 eV 处的峰被分配给 Cu+ 或 Cu 0,933.92 和 954.62 eV 处的峰被分配给 Cu2+，（22,23,48），这意味着合成的 CSA 纳米颗粒中铜元素的价态混合。对于 Se 3d 的高分辨率 XPS（图 1I），53.8 和 53.3 eV 处的峰分别对应于 Se 3d3/2 和 Se 3d5/2,57.8 eV 处的峰是由于 SeOx 引起的。（49−51） 在 Ag 3d 光谱（图 1J）中，368.5 和 374.5 eV 处峰的出现分别标于 Ag 3d5/2 和 Ag 3d3/2，表明 Ag 的价态为零，并且在 CS 表面形成纯金属 Ag。（52,53） 这些结果表明，制备的 CSA 具有生物医学应用的理想特性。 此外，CSA 中 Cu（I） 和 Cu（II） 的存在可能有利于在弱酸性条件下实现模拟活性。
2.2. Inhibition of TrxR Activity and GSH Consumption
2.2. 抑制 TrxR 活性和 GSH 消耗
Due to the presence of high-valent Cu2+ and Se–Se bonds in CSA, CSA have the potential to deplete GSH and inhibit TrxR. TrxR, which is a selenoprotein, has emerged as an important molecular target for anticancer drug development. Selenium nanoparticles could target the Sec residue of TrxR to inhibit the activity of TrxR and disturb cellular redox homeostasis, reinforcing ROS cytotoxicity. (15) In order to assess TrxR activities after reacting with CS, an activity assay using direct reduction of 5,5′-dithio-bis(2-nitrobenzoic acid) (DTNB) was employed. As evidenced in Figure S5, TrxR activity decreased with increasing CS concentration, illustrating that CS could inhibit TrxR activity. As presented in Figure 2A, the CSA group exhibited more obvious TrxR inhibition than CS under the same concentration due to the modified AgNPs, which could inhibit selenoprotein synthesis and inhibition of TrxR1. (42) To confirm the capability of CSA to deplete GSH, DTNB was used as a probe, which could react with sulfhydryl of GSH to form yellow 2-nitro-5-thiobenzoic acid (TNB) with a characteristic absorption peak at 412 nm. Upon GSH reaction with CSA or CS, the absorption at 412 nm was decreased with the increase of time (Figures 2B and S6), suggesting the potential of CSA and CS to lower the GSH level. In order to further investigate that CSA could deplete GSH, XPS on CSA reacted with GSH was performed. As illustrated in Figure S7, after CSA reacted with GSH, the satellite peak of Cu2+ weakened evidently in comparison with that of CSA without reacting with GSH. (51) These results confirmed that the CSA could reduce the GSH level and inhibit TrxR activity and has the potential to boost the oxidative stress in tumors, thereby improving the catalytic treatment efficiency.
由于 CSA 中存在高价 Cu2+ 和 Se-Se 键，CSA 有可能消耗 GSH 并抑制 TrxR。TrxR 是一种硒蛋白，已成为抗癌药物开发的重要分子靶点。硒纳米颗粒可以靶向 TrxR 的 Sec 残基，抑制 TrxR 的活性并扰乱细胞氧化还原稳态，增强 ROS 细胞毒性。（15） 为了评估与 CS 反应后的 TrxR 活性，采用了使用直接还原 5,5′-二硫代-双（2-硝基苯甲酸）（DTNB） 的活性测定。如图 S5 所示，TrxR 活性随着 CS 浓度的增加而降低，表明 CS 可以抑制 TrxR 活性。如图 2A 所示，由于修饰的 AgNPs，在相同浓度下，CSA 组表现出比 CS 更明显的 TrxR 抑制作用，可以抑制硒蛋白合成和抑制 TrxR1。（42） 为了证实 CSA 消耗 GSH 的能力，以 DTNB 为探针，可与 GSH 的巯基反应生成黄色 2-硝基-5-硫代苯甲酸 （TNB），在 412 nm 处具有特征吸收峰。与 CSA 或 CS 反应后，412 nm 处的吸收随着时间的增加而降低（图 2B 和 S6），表明 CSA 和 CS 有可能降低 GSH 水平。为了进一步研究 CSA 可以消耗 GSH，对 CSA 与 GSH 反应进行了 XPS。如图 S7 所示，CSA 与 GSH 反应后，Cu2+ 的卫星峰与未与 GSH 反应的 CSA 相比明显减弱。 （51） 这些结果证实，CSA 可以降低 GSH 水平并抑制 TrxR 活性，并有可能提高肿瘤中的氧化应激，从而提高催化治疗效率。
由于 CSA 中存在高价 Cu2+ 和 Se-Se 键，CSA 有可能消耗 GSH 并抑制 TrxR。TrxR 是一种硒蛋白，已成为抗癌药物开发的重要分子靶点。硒纳米颗粒可以靶向 TrxR 的 Sec 残基，抑制 TrxR 的活性并扰乱细胞氧化还原稳态，增强 ROS 细胞毒性。（15） 为了评估与 CS 反应后的 TrxR 活性，采用了使用直接还原 5,5′-二硫代-双（2-硝基苯甲酸）（DTNB） 的活性测定。如图 S5 所示，TrxR 活性随着 CS 浓度的增加而降低，表明 CS 可以抑制 TrxR 活性。如图 2A 所示，由于修饰的 AgNPs，在相同浓度下，CSA 组表现出比 CS 更明显的 TrxR 抑制作用，可以抑制硒蛋白合成和抑制 TrxR1。（42） 为了证实 CSA 消耗 GSH 的能力，以 DTNB 为探针，可与 GSH 的巯基反应生成黄色 2-硝基-5-硫代苯甲酸 （TNB），在 412 nm 处具有特征吸收峰。与 CSA 或 CS 反应后，412 nm 处的吸收随着时间的增加而降低（图 2B 和 S6），表明 CSA 和 CS 有可能降低 GSH 水平。为了进一步研究 CSA 可以消耗 GSH，对 CSA 与 GSH 反应进行了 XPS。如图 S7 所示，CSA 与 GSH 反应后，Cu2+ 的卫星峰与未与 GSH 反应的 CSA 相比明显减弱。 （51） 这些结果证实，CSA 可以降低 GSH 水平并抑制 TrxR 活性，并有可能提高肿瘤中的氧化应激，从而提高催化治疗效率。
Figure 2 图 2
Figure 2. (A) Relative activity of TrxR enzyme with the treatment of different amounts of CSA (n = 3). (B) Time-dependent UV/vis absorption changes of DTNB treated with CSA (50 μg/mL) in a PBS solution containing GSH (10 mM). (C) Photothermal heating curves of CSA with different concentrations under 1064 nm laser (1.0 W/cm2). (D) Temperature curves of CSA (50 μg/mL) with a 1064 nm laser of different power irradiation for different times. (E) Recycling–heating profiles of CSA solution (50 μg/mL) under cyclic on/off laser irradiation. (F) Temperature elevation and cooling curves of CSA solution (50 μg/mL) after 5 min of irradiation (1.0 W/cm2) and linear regression data obtained from the cooling period. ESR spectra of (G) DMPO/•OH, (H) DMPO/•O2–, and (I) TEMP/1O2, treated with H2O2, CSA, or NIR irradiation under different conditions.
图 2.（A） TrxR 酶在不同量 CSA 处理下的相对活性 （n = 3）。（B） 在含 GSH （10 mM） 的 PBS 溶液中，CSA （50 μg/mL） 处理的 DTNB 的随时间变化的紫外可见光吸收变化。（C） 不同浓度 CSA 在 1064 nm 激光 （1.0 W/cm2） 下的光热加热曲线。（D） 不同功率激光照射不同时间的 CSA （50 μg/mL） 的温度曲线。（E） CSA 溶液 （50 μg/mL） 在循环开/关激光照射下的回收-加热曲线。（F） 照射 5 分钟 （1.0 W/cm2） 后 CSA 溶液 （50 μg/mL） 的温度升高和冷却曲线以及从冷却期获得的线性回归数据。（G） DMPO/•OH、（H） DMPO/•O 2– 和 （I） TEMP/1O2 在不同条件下用 H2O2、CSA 或 NIR 照射处理的 ESR 光谱。
2.3. Photothermal Properties of CSA
2.3. CSA 的光热特性
In order to study the photothermal performance triggered by 1064 nm, the absorption capacity of CSA in the NIR region was first measured, and the result is shown in Figure S8. It can be seen that CSA exhibited absorption in the full spectrum and even in the NIR region superior to CS. This enhanced absorption may be due to the abundant active sites and modified AgNPs, which could enhance the absorption and utilization of laser irradiation. In order to further investigate the optical characteristics of CSA, UV–vis diffuse reflectance spectroscopy (UV–vis DRS) was employed. As displayed in Figure S9, CSA exhibited higher absorption intensities compared to that of CS and shows a wide absorption band in the region of 470–750 nm, which is attributed to the SPR absorption of Ag species. (37,54,55)
为了研究 1064 nm 触发的光热性能，首先测量了 CSA 在 NIR 区域的吸收能力，结果如图 S8 所示。可以看出，CSA 在全光谱中表现出吸收能力，甚至在 NIR 区域也优于 CS。这种增强的吸收可能是由于丰富的活性位点和修饰的 AgNPs，这可能会增强激光照射的吸收和利用。为了进一步研究 CSA 的光学特性，采用了紫外-可见漫反射光谱 （UV-vis DRS）。如图 S9 所示，与 CS 相比，CSA 表现出更高的吸收强度，并且在 470-750 nm 范围内显示出较宽的吸收带，这归因于 Ag 物质的 SPR 吸收。（37,54,55）
为了研究 1064 nm 触发的光热性能，首先测量了 CSA 在 NIR 区域的吸收能力，结果如图 S8 所示。可以看出，CSA 在全光谱中表现出吸收能力，甚至在 NIR 区域也优于 CS。这种增强的吸收可能是由于丰富的活性位点和修饰的 AgNPs，这可能会增强激光照射的吸收和利用。为了进一步研究 CSA 的光学特性，采用了紫外-可见漫反射光谱 （UV-vis DRS）。如图 S9 所示，与 CS 相比，CSA 表现出更高的吸收强度，并且在 470-750 nm 范围内显示出较宽的吸收带，这归因于 Ag 物质的 SPR 吸收。（37,54,55）
Upon 1064 nm laser irradiation for 5 min, the temperatures of CSA (45 μg/mL) increased from 30.2 to 55.2 °C (Figure S10), while PBS only increased by 5.0 °C (Figure 2C), suggesting the good photothermal conversion ability of CSA. Moreover, the temperature of CSA increased under 1064 nm laser at varying concentrations and laser power densities (Figure 2C,D). These results elucidated that CSA exhibits a concentration-, excitation time-, and laser power density-dependent elevated temperature behavior. After six cycles of illumination, no significant change was observed in the temperature increase of CSA, illustrating that CSA exhibited excellent photothermal stability (Figure 2E). Subsequently, the photothermal conversion efficiency (PTCE) was determined by analyzing the linear regression curve of the thermal cooling process. According to calculations, the corresponding PTCE (sηT) of CSA was calculated to be 52.7%. All of these results suggested that CSA possesses significant photothermal conversion capability and has immense potential for photothermal therapy (PTT) application.
1064 nm 激光照射 5 分钟后，CSA （45 μg/mL） 的温度从 30.2 °C 增加到 55.2 °C（图 S10），而 PBS 仅升高了 5.0 °C（图 2C），表明 CSA 具有良好的光热转换能力。此外，在不同浓度和激光功率密度的 1064 nm 激光下，CSA 的温度升高（图 2C，D）。这些结果表明，CSA 表现出与浓度、激发时间和激光功率密度相关的高温行为。经过 6 次照明循环后，未观察到 CSA 的温度升高发生显着变化，表明 CSA 表现出优异的光热稳定性（图 2E）。随后，通过分析热冷却过程的线性回归曲线来确定光热转换效率 （PTCE）。根据计算，CSA 的相应 PTCE （sηT） 计算为 52.7%。所有这些结果表明，CSA 具有显着的光热转换能力，并且在光热疗法 （PTT） 应用方面具有巨大的潜力。
1064 nm 激光照射 5 分钟后，CSA （45 μg/mL） 的温度从 30.2 °C 增加到 55.2 °C（图 S10），而 PBS 仅升高了 5.0 °C（图 2C），表明 CSA 具有良好的光热转换能力。此外，在不同浓度和激光功率密度的 1064 nm 激光下，CSA 的温度升高（图 2C，D）。这些结果表明，CSA 表现出与浓度、激发时间和激光功率密度相关的高温行为。经过 6 次照明循环后，未观察到 CSA 的温度升高发生显着变化，表明 CSA 表现出优异的光热稳定性（图 2E）。随后，通过分析热冷却过程的线性回归曲线来确定光热转换效率 （PTCE）。根据计算，CSA 的相应 PTCE （sηT） 计算为 52.7%。所有这些结果表明，CSA 具有显着的光热转换能力，并且在光热疗法 （PTT） 应用方面具有巨大的潜力。
2.4. ROS Generation of CSA NPs
2.4. CSA NP 的 ROS 生成
It is widely recognized that copper-based materials exhibited excellent catalytic activity and had various applications as nanozymes. In order to investigate the Fenton-like activity of CS and CSA, 3,3′,5,5′-Tetramethylbenzidine (TMB) was chosen as an indicator, which could be oxidized to generate the blue substrate oxTMB. oxTMB presents a characteristic absorption band at ∼650 nm, indicating •OH generation. As demonstrated in Figure S11, compared to the presence of only TMB or H2O2, the absorbance of oxTMB at 650 nm significantly increased in the presence of H2O2 and CS or CSA, suggesting the generation of •OH via the Fenton-like reaction. Besides, fluorescence spectroscopy utilizing terephthalic acid as a probe also confirmed the generation of •OH (Figure S12). Furthermore, the •OH generation was further validated by electron spin resonance (ESR) spectroscopy employing 5,5-dimethyl-1- pyrroline-N-oxide (DMPO) as the capture agent. As presented in Figure 2G, strong characteristic signals of a 1:2:2:1 line shape appeared in the system of “CSA + H2O2”, indicating the generation of •OH. Upon laser irradiation, the peak intensity of •OH increased in comparison to the group of “CSA + H2O2” without laser irradiation, showing that NIR-II could improve the production of •OH. Then, in order to identify whether other ROS such as 1O2, •O2–, and H2O2 were generated in the mimicking catalytic process, the •O2– probe dihydroethidium (DHE), the 1O2 probe 2,2′-(anthracene-9,10-diyldimethanediyl)dipropanedioic acid (ABDA), and the H2O2 amplex red were utilized. As illustrated in Figure S13A, the absorbance of ABDA decreased with the reaction time increasing, suggesting 1O2 generation. While the absorbance of ABDA exhibited insignificant change in the N2-saturated PBS (Figure S13B). Compared to the control, the fluorescence intensity of DHE increased in the presence of CSA, suggesting •O2– generation (Figure S14). In the presence of CSA, the fluorescence intensity of amplex red increased in the presence of O2 compared to that in N2, indicating H2O2 generation (Figure S15). Then, EPR tests were conducted to clarify the formed •O2– and 1O2 by using DMPO and 2,2,6,6-tetramethyl-4-piperidine (TEMP) as the trapping probe, respectively. As displayed in Figure 2H, CSA induced the generation of a four-line spectrum with relative intensities of 1:1:1:1, which was the characteristic spectrum of •O2–. Furthermore, a strong characteristic peak of 1:1:1 was observed in the groups of “CSA + H2O2”, indicative of the presence of 1O2 (Figure 2I). Significantly enhanced characteristic peaks were discovered in the group of “CSA + laser + H2O2” after laser irradiation for 5 min, manifesting the highest production of 1O2. As shown in Figure S16, CS displayed weaker signals of •OH, •O2–, and 1O2 than CSA, demonstrating that AgNP-modified CS could generate more ROS than CS via photocatalysis, attributed to the SPR of AgNPs. These results validated that CSA indeed has the potential to generate •OH, O2•–, and 1O2 and that its catalytic activity could be enhanced by laser irradiation. The possibly catalytic mechanisms can be described as follows (22,56,57)
人们普遍认为，铜基材料表现出优异的催化活性，并作为纳米酶具有多种应用。为了研究 CS 和 CSA 的 Fenton 样活性，选择 3,3'，5,5'-四甲基联苯胺 （TMB） 作为指示剂，其可被氧化生成蓝色底物 oxTMB。oxTMB 在 ∼650 nm 处呈现特征吸收带，表明 •OH 产生。如图 S11 所示，与仅存在 TMB 或 H2O2 相比，在 H2O2 和 CS 或 CSA 存在下，oxTMB 在 650 nm 处的吸光度显著增加，表明通过芬顿样反应生成 •OH。此外，使用对苯二甲酸作为探针的荧光光谱也证实了 •OH 的产生（图 S12）。此外，采用 5,5-二甲基-1-吡咯啉-N-氧化物 （DMPO） 作为捕获剂的电子自旋共振 （ESR） 光谱进一步验证了 •OH 的产生。如图 2G 所示，“CSA + H2O2”系统中出现 1：2：2：1 线形的强特征信号，表明 •OH 的产生。与未进行激光照射的“CSA + H2O2”组相比，激光照射后 •OH 的峰值强度增加，表明 NIR-II 可以改善 •OH 的产生。 然后，为了确定在模拟催化过程中是否产生了其他 ROS，如 1O2、•O2– 和 H2O2，使用了•O2– 探针二氢乙锭 （DHE）、1O2 探针 2,2′-（蒽-9,10-二基二甲烷二基）二丙二酸 （ABDA） 和 H2O2 amplex red。如图 S13A 所示，ABDA 的吸光度随着反应时间的增加而降低，表明产生 1O2。而 ABDA 的吸光度在 N2 饱和 PBS 中表现出不显着的变化（图 S13B）。与对照相比，在 CSA 存在下 DHE 的荧光强度增加，表明 •O2 – 产生（图 S14）。在 CSA 存在下，与 N2 相比，在 O2 存在下 amplex red 的荧光强度增加，表明 H2O2 产生（图 S15）。然后，分别使用 DMPO 和 2,2,6,6-四甲基-4-哌啶 （TEMP） 作为捕获探针进行 EPR 测试以澄清形成的 •O2– 和 1O2。如图 2H 所示，CSA 诱导产生相对强度为 1：1：1：1 的四线光谱，这是 •O2– 的特征光谱。此外，在“CSA + H2O2”组中观察到 1：1：1 的强特征峰，表明存在 1O2（图 2I）。 激光照射 5 min 后，“CSA + 激光 + H2O2”组发现特征峰显著增强，表现为 1O2 的最高产量。如图 S16 所示，CS 显示出比 CSA 弱的 •OH、•O2– 和 1O2 信号，这表明 AgNP 修饰的 CS 可以通过光催化产生比 CS 更多的 ROS，这归因于 AgNPs 的 SPR。这些结果验证了 CSA 确实具有产生 •OH、O2•– 和 1O2 的潜力，并且其催化活性可以通过激光照射增强。可能的催化机制可以描述如下 （22,56,57）In the catalytic system of CSA, H2O2 was adsorbed on the CSA surface and activated by Cu(I) in CSA, leading to the generation of •OH, while simultaneously oxidizing Cu(I) to Cu(II). The generated •OH reacted with excess H2O2 to generate •O2–. Subsequently, generated •O2– reacted with H2O to generate 1O2 and H2O2, revealing the H2O2 cycling in the system. On the other hand, the generated •O2– was further oxidized into 1O2 along with Cu(II) reduced back to Cu(I), achieving the Cu(II)/Cu(I) redox cycling. Additionally, due to the SPR effects of AgNPs, the AgNPs on the surface of CS could enhance the efficiency of the charge reaction and capture electrons that underwent electron transfer with the surrounding O2 to produce •O2–, thereby accelerating the generation of ROS. This process underscores the potential of CSA as a potent catalyst in relevant reactions. Furthermore, the effect of pH and temperature on the catalyst activity of CSA as well as their catalytic stability under physiological conditions was studied (Figure S17). It can be seen that CSA exhibited excellent enzymatic activity under physiological conditions, implying its potential application for subsequent cancer therapy.
在 CSA 的催化体系中，H2O2 吸附在 CSA 表面并被 CSA 中的 Cu（I） 活化，导致 •OH 的生成，同时将 Cu（I） 氧化成 Cu（II）。生成的 •OH 与过量的 H2O2 反应生成 •O2–。随后，生成的 •O2– 与 H2O 反应生成 1O2 和 H2O2，揭示了系统中的 H2O2 循环。另一方面，生成的 •O2– 进一步氧化成 1O2 以及 Cu（II） 还原回 Cu（I），实现 Cu（II）/Cu（I） 氧化还原循环。此外，由于 AgNPs 的 SPR 效应，CS 表面的 AgNPs 可以提高电荷反应的效率，并捕获与周围 O2 发生电子转移的电子以产生 •O2–，从而加速 ROS 的产生。这一过程强调了 CSA 作为相关反应中有效催化剂的潜力。此外，还研究了 pH 值和温度对 CSA 催化剂活性及其在生理条件下催化稳定性的影响（图 S17）。由此可见，CSA 在生理条件下表现出优异的酶活性，暗示其在后续癌症治疗中的潜在应用。
人们普遍认为，铜基材料表现出优异的催化活性，并作为纳米酶具有多种应用。为了研究 CS 和 CSA 的 Fenton 样活性，选择 3,3'，5,5'-四甲基联苯胺 （TMB） 作为指示剂，其可被氧化生成蓝色底物 oxTMB。oxTMB 在 ∼650 nm 处呈现特征吸收带，表明 •OH 产生。如图 S11 所示，与仅存在 TMB 或 H2O2 相比，在 H2O2 和 CS 或 CSA 存在下，oxTMB 在 650 nm 处的吸光度显著增加，表明通过芬顿样反应生成 •OH。此外，使用对苯二甲酸作为探针的荧光光谱也证实了 •OH 的产生（图 S12）。此外，采用 5,5-二甲基-1-吡咯啉-N-氧化物 （DMPO） 作为捕获剂的电子自旋共振 （ESR） 光谱进一步验证了 •OH 的产生。如图 2G 所示，“CSA + H2O2”系统中出现 1：2：2：1 线形的强特征信号，表明 •OH 的产生。与未进行激光照射的“CSA + H2O2”组相比，激光照射后 •OH 的峰值强度增加，表明 NIR-II 可以改善 •OH 的产生。 然后，为了确定在模拟催化过程中是否产生了其他 ROS，如 1O2、•O2– 和 H2O2，使用了•O2– 探针二氢乙锭 （DHE）、1O2 探针 2,2′-（蒽-9,10-二基二甲烷二基）二丙二酸 （ABDA） 和 H2O2 amplex red。如图 S13A 所示，ABDA 的吸光度随着反应时间的增加而降低，表明产生 1O2。而 ABDA 的吸光度在 N2 饱和 PBS 中表现出不显着的变化（图 S13B）。与对照相比，在 CSA 存在下 DHE 的荧光强度增加，表明 •O2 – 产生（图 S14）。在 CSA 存在下，与 N2 相比，在 O2 存在下 amplex red 的荧光强度增加，表明 H2O2 产生（图 S15）。然后，分别使用 DMPO 和 2,2,6,6-四甲基-4-哌啶 （TEMP） 作为捕获探针进行 EPR 测试以澄清形成的 •O2– 和 1O2。如图 2H 所示，CSA 诱导产生相对强度为 1：1：1：1 的四线光谱，这是 •O2– 的特征光谱。此外，在“CSA + H2O2”组中观察到 1：1：1 的强特征峰，表明存在 1O2（图 2I）。 激光照射 5 min 后，“CSA + 激光 + H2O2”组发现特征峰显著增强，表现为 1O2 的最高产量。如图 S16 所示，CS 显示出比 CSA 弱的 •OH、•O2– 和 1O2 信号，这表明 AgNP 修饰的 CS 可以通过光催化产生比 CS 更多的 ROS，这归因于 AgNPs 的 SPR。这些结果验证了 CSA 确实具有产生 •OH、O2•– 和 1O2 的潜力，并且其催化活性可以通过激光照射增强。可能的催化机制可以描述如下 （22,56,57）
(1)
(2)
(3)
(4)
在 CSA 的催化体系中，H2O2 吸附在 CSA 表面并被 CSA 中的 Cu（I） 活化，导致 •OH 的生成，同时将 Cu（I） 氧化成 Cu（II）。生成的 •OH 与过量的 H2O2 反应生成 •O2–。随后，生成的 •O2– 与 H2O 反应生成 1O2 和 H2O2，揭示了系统中的 H2O2 循环。另一方面，生成的 •O2– 进一步氧化成 1O2 以及 Cu（II） 还原回 Cu（I），实现 Cu（II）/Cu（I） 氧化还原循环。此外，由于 AgNPs 的 SPR 效应，CS 表面的 AgNPs 可以提高电荷反应的效率，并捕获与周围 O2 发生电子转移的电子以产生 •O2–，从而加速 ROS 的产生。这一过程强调了 CSA 作为相关反应中有效催化剂的潜力。此外，还研究了 pH 值和温度对 CSA 催化剂活性及其在生理条件下催化稳定性的影响（图 S17）。由此可见，CSA 在生理条件下表现出优异的酶活性，暗示其在后续癌症治疗中的潜在应用。
2.5. In Vitro Response of CSA
2.5. CSA 的体外反应
Prior to investigating the in vitro response of CSA, it was first modified with fluorescein isothiocyanate (FITC) to explore the cellular endocytosis. As depicted in Figure S18, following incubation with A549 cells (a human lung cancer cell line) for a prolonged time (2, 4, 6, 8, and 10 h), the green fluorescence intensity was observed to increase with the incubation time, implying effective cellular uptake for further therapeutic applications. Given the excellent catalytic activity of the synthesized CSA nanozyme, the in vitro therapeutic activity of CSA was evaluated. Subsequently, the cytotoxicity of CS and CSA was evaluated using the CCK-8 assay with A549 cells. As depicted in Figures S19 and 3A, both CS and CSA showed significant cytotoxicity and exhibited dose-dependent cytotoxicity toward A549 cells, which could be attributed to the potent redox effect of CSA and CS, along with the depletion of GSH and the inhibition of TrxR. Comparatively, CSA exhibited lower toxicity in normal cells (Figure S20). Upon treatment with a 1064 nm laser (1.0 W/cm2, 5 min), cell inhibition was significantly enhanced in comparison with the absence of irradiation, implying the superior therapeutic effect of PTT and photocatalytic therapy. To further evaluate cell viability, confocal laser scanning microscopy (CLSM) imaging was utilized by staining A549 cells with calcein-AM and PI cell staining assays after various treatments (Figure 3B). It can be seen that the most obvious dead cells appeared in the CSA group. Compared to the group without laser irradiation, CSA with NIR-II irradiation exhibited obviously increased apoptosis, which showed evident concentration dependence and demonstrated a notable synergistic therapeutic effect. Collectively, these investigations implied that CSA could be as an excellent nanogent for enhancing cancer cell apoptosis under NIR excitation.
在研究 CSA 的体外反应之前，首先用异硫氰酸荧光素 （FITC） 修饰它以探索细胞内吞作用。如图 S18 所示，与 A549 细胞（一种人肺癌细胞系）长时间孵育后（2、4、6、8 和 10 小时），观察到绿色荧光强度随着孵育时间的增加而增加，这意味着细胞有效摄取用于进一步的治疗应用。鉴于合成的 CSA 纳米酶具有出色的催化活性，评价了 CSA 的体外治疗活性。随后，使用 A549 细胞的 CCK-8 测定评估 CS 和 CSA 的细胞毒性。如图 S19 和 3A 所示，CS 和 CSA 均显示出显着的细胞毒性，并且对 A549 细胞表现出剂量依赖性细胞毒性，这可能归因于 CSA 和 CS 的有效氧化还原效应，以及 GSH 的消耗和 TrxR 的抑制。相比之下，CSA 在正常细胞中表现出较低的毒性（图 S20）。用 1064 nm 激光 （1.0 W/cm2， 5 min） 处理后，与没有照射相比，细胞抑制显着增强，这意味着 PTT 和光催化疗法的治疗效果优越。为了进一步评估细胞活力，在各种处理后用钙黄绿素-AM 和 PI 细胞染色测定法对 A549 细胞进行染色，利用共聚焦激光扫描显微镜 （CLSM） 成像（图 3B）。可以看出，最明显的死细胞出现在 CSA 组中。与未激光照射组相比，NIR-II 照射的 CSA 细胞凋亡明显增加，表现出明显的浓度依赖性，并显示出显着的协同治疗效果。 总的来说，这些研究表明 CSA 可以作为一种在 NIR 激发下增强癌细胞凋亡的优秀纳米剂。
在研究 CSA 的体外反应之前，首先用异硫氰酸荧光素 （FITC） 修饰它以探索细胞内吞作用。如图 S18 所示，与 A549 细胞（一种人肺癌细胞系）长时间孵育后（2、4、6、8 和 10 小时），观察到绿色荧光强度随着孵育时间的增加而增加，这意味着细胞有效摄取用于进一步的治疗应用。鉴于合成的 CSA 纳米酶具有出色的催化活性，评价了 CSA 的体外治疗活性。随后，使用 A549 细胞的 CCK-8 测定评估 CS 和 CSA 的细胞毒性。如图 S19 和 3A 所示，CS 和 CSA 均显示出显着的细胞毒性，并且对 A549 细胞表现出剂量依赖性细胞毒性，这可能归因于 CSA 和 CS 的有效氧化还原效应，以及 GSH 的消耗和 TrxR 的抑制。相比之下，CSA 在正常细胞中表现出较低的毒性（图 S20）。用 1064 nm 激光 （1.0 W/cm2， 5 min） 处理后，与没有照射相比，细胞抑制显着增强，这意味着 PTT 和光催化疗法的治疗效果优越。为了进一步评估细胞活力，在各种处理后用钙黄绿素-AM 和 PI 细胞染色测定法对 A549 细胞进行染色，利用共聚焦激光扫描显微镜 （CLSM） 成像（图 3B）。可以看出，最明显的死细胞出现在 CSA 组中。与未激光照射组相比，NIR-II 照射的 CSA 细胞凋亡明显增加，表现出明显的浓度依赖性，并显示出显着的协同治疗效果。 总的来说，这些研究表明 CSA 可以作为一种在 NIR 激发下增强癌细胞凋亡的优秀纳米剂。
Figure 3 图 3
Figure 3. (A) Cell viability of A549 cells treated with different concentrations of CSA under different conditions. Error bars represent standard deviation for n = 5; P values were based on Student’s t-test: ****P < 0.0001, ***P < 0.001, **P < 0.01, and *P < 0.05. (B) Fluorescence images of calcein AM (green, live cells, Ex = 488 nm) and PI (red, dead cells, Ex = 552 nm) costained A549 cells after incubation with various concentrations of CSA for 24 h. Scale bars: 250 μm. (C) Confocal microscopy images of A549 cells with HPF, DHE, and SOSG to study the •OH, •O2–, and 1O2 generation, respectively, in the presence of CSA (15 μg/mL) with or without laser (Ex = 488 nm). Scale bars: 50 μm.
图 3.（A） 在不同条件下用不同浓度的 CSA 处理的 A549 细胞的细胞活力。误差线表示 n = 5 的标准差;P 值基于学生 t 检验：******P < 0.0001，***P < 0.001，**P < 0.01，*P < 0.05。（B） 钙黄绿素 AM （绿色，活细胞，Ex = 488 nm） 和 PI （红色，死细胞，Ex = 552 nm） 共染色 A549 细胞与不同浓度的 CSA 孵育 24 小时后的荧光图像。比例尺：250 μm。（C） 使用 HPF、DHE 和 SOSG 对 A549 细胞进行共聚焦显微镜成像，分别研究在 CSA （15 μg/mL） 存在下（有或没有激光 （Ex = 488 nm） 的 •OH、•O2 和 1O2 代。比例尺：50 μm。
Furthermore, in order to confirm the generation of ROS within the cell, a series of fluorescence probes including hydroxyphenyl fluorescein (HPF), dihydroethidium (DHE), and singlet oxygen sensor green (SOSG) were employed to indicate the generation of •OH, •O2–, and 1O2, respectively, using CLSM. As illustrated in Figures 3C and S21, compared to the control, a weaker fluorescence was observed in the CS and CSA groups, indicating less ROS generation. However, the fluorescence was increased in the presence of NIR-II irradiation, which was attributed to the enhancement of catalytic activity for the ROS generation. This observation underscores the potential of NIR-II irradiation in boosting the catalytic activity of CSA, thereby facilitating ROS generation.
此外，为了确认细胞内 ROS 的产生，采用一系列荧光探针，包括羟苯基荧光素 （HPF）、二氢乙锭 （DHE） 和单线态氧传感器绿色 （SOSG） 来指示 •OH、•O2– 和 1O2 的产生，分别使用 CLSM。如图 3C 和 S21 所示，与对照组相比，在 CS 和 CSA 组中观察到较弱的荧光，表明 ROS 生成较少。然而，在 NIR-II 照射存在下荧光增加，这归因于 ROS 生成的催化活性增强。这一观察结果强调了 NIR-II 辐照在提高 CSA 催化活性方面的潜力，从而促进 ROS 的产生。
此外，为了确认细胞内 ROS 的产生，采用一系列荧光探针，包括羟苯基荧光素 （HPF）、二氢乙锭 （DHE） 和单线态氧传感器绿色 （SOSG） 来指示 •OH、•O2– 和 1O2 的产生，分别使用 CLSM。如图 3C 和 S21 所示，与对照组相比，在 CS 和 CSA 组中观察到较弱的荧光，表明 ROS 生成较少。然而，在 NIR-II 照射存在下荧光增加，这归因于 ROS 生成的催化活性增强。这一观察结果强调了 NIR-II 辐照在提高 CSA 催化活性方面的潜力，从而促进 ROS 的产生。
Based on the generated ROS and the interaction of CSA with biological molecules including GSH, lipid, and TrxR, glutathione peroxidase 4 (GPX4), several fluorescent probes such as C11-BODIPY581/591, and TRFs-green as a fluorescent probe were employed to measure the changes in the intracellular GSH level, lipid peroxidation (LPO), and TrxR level, respectively, using CLSM. As shown in Figure S22, the intracellular GSH levels gradually decreased with increasing CSA concentration with further reductions observed under laser irradiation at the same CSA concentrations. It is well established that intracellular GSH depletion is accompanied by the inactivation of GPX4. As illustrated in Figure 4A, the green fluorescence intensity decreased with the increase in incubation CSA, suggesting a decrease in GPX4 expressions in cells. Moreover, the expression of GPX4 in cells after treatment with CSA under laser irradiation was significantly decreased in comparison with the cell only treated with CSA. Because CSA could inhibit the activity of TrxR, the viability of TrxR in cells was assessed via the TrxR assay kit. The results displayed that incubation of A549 cells with CSA drastically reduced the TrxR activity (Figure S23). Incubation of A549 cells with CSA and treatment with laser irradiation could further reduce the TrxR activity compared to that observed in the presence of only CSA. Furthermore, fluorescence images of TrxR expressed by A549 cells after different treatments were recorded and are presented in Figure 4B. Obviously, the expression of TrxR in A549 cells after incubating with CSA nanoparticles under laser irradiation was significantly decreased in comparison with cells treated with CSA. These results demonstrated that CSA could induce GSH depletion and inhibit TrxR activity.
基于生成的 ROS 和 CSA 与 GSH 、脂质和 TrxR、谷胱甘肽过氧化物酶 4 （GPX4） 等生物分子的相互作用，采用 C11-BODIPY581/591 和 TRFs-green 等几种荧光探针作为荧光探针，分别使用 CLSM 测量细胞内 GSH 水平、脂质过氧化 （LPO） 和 TrxR 水平的变化。如图 S22 所示，细胞内 GSH 水平随着 CSA 浓度的增加而逐渐降低，在相同 CSA 浓度的激光照射下观察到进一步降低。众所周知，细胞内 GSH 耗竭伴随着 GPX4 的失活。如图 4A 所示，绿色荧光强度随着孵育 CSA 的增加而降低，表明细胞中 GPX4 表达降低。此外，与仅用 CSA 处理的细胞相比，在激光照射下用 CSA 处理后细胞中 GPX4 的表达显著降低。由于 CSA 可以抑制 TrxR 的活性，因此通过 TrxR 检测试剂盒评估 TrxR 在细胞中的活力。结果表明，A549 细胞与 CSA 的孵育大大降低了 TrxR 活性（图 S23）。与仅在 CSA 存在下观察到的相比，A549 细胞与 CSA 孵育和激光照射处理可以进一步降低 TrxR 活性。此外，记录了不同处理后 A549 细胞表达的 TrxR 的荧光图像，如图 4B 所示。显然，与用 CSA 处理的细胞相比，在激光照射下与 CSA 纳米颗粒孵育后，A549 细胞中 TrxR 的表达显着降低。 这些结果表明，CSA 可以诱导 GSH 耗竭并抑制 TrxR 活性。
基于生成的 ROS 和 CSA 与 GSH 、脂质和 TrxR、谷胱甘肽过氧化物酶 4 （GPX4） 等生物分子的相互作用，采用 C11-BODIPY581/591 和 TRFs-green 等几种荧光探针作为荧光探针，分别使用 CLSM 测量细胞内 GSH 水平、脂质过氧化 （LPO） 和 TrxR 水平的变化。如图 S22 所示，细胞内 GSH 水平随着 CSA 浓度的增加而逐渐降低，在相同 CSA 浓度的激光照射下观察到进一步降低。众所周知，细胞内 GSH 耗竭伴随着 GPX4 的失活。如图 4A 所示，绿色荧光强度随着孵育 CSA 的增加而降低，表明细胞中 GPX4 表达降低。此外，与仅用 CSA 处理的细胞相比，在激光照射下用 CSA 处理后细胞中 GPX4 的表达显著降低。由于 CSA 可以抑制 TrxR 的活性，因此通过 TrxR 检测试剂盒评估 TrxR 在细胞中的活力。结果表明，A549 细胞与 CSA 的孵育大大降低了 TrxR 活性（图 S23）。与仅在 CSA 存在下观察到的相比，A549 细胞与 CSA 孵育和激光照射处理可以进一步降低 TrxR 活性。此外，记录了不同处理后 A549 细胞表达的 TrxR 的荧光图像，如图 4B 所示。显然，与用 CSA 处理的细胞相比，在激光照射下与 CSA 纳米颗粒孵育后，A549 细胞中 TrxR 的表达显着降低。 这些结果表明，CSA 可以诱导 GSH 耗竭并抑制 TrxR 活性。
Figure 4 图 4
Figure 4. CLSM images of (A) GPX4, (B) TRFS-green, (C) C11-BODIPY581/591, (D) TF2-DEVD-FMK, and (E) AO-stained A549 cells treated with CSA at different concentrations. Scale bars: 50 μm.
Based on the generation of ROS that could induce the LPO of lysosomal membrane, the C11-BODIPY581/591 probe was used to elucidate CSA-triggered LPO, and the results are shown in Figure 4C. The result showed that the intensity of red fluorescence decreased with an increase in CSA concentration, while the intensity of green fluorescence increased, confirming that the lipids of cells incubated with CSA were severely peroxided. In addition, the expression level of cleaved caspase-3, a marker of apoptosis, was measured using CLSM. The results displayed an increase in the green fluorescence intensity in cells incubated with CSA with or without laser irradiation treatment (Figure 4D), implying the induction of apoptosis in the cells.
基于可诱导溶酶体膜 LPO 的 ROS 的产生，使用 C11-BODIPY581/591 探针阐明 CSA 触发的 LPO，结果如图 4C 所示。结果显示，红色荧光强度随 CSA 浓度的增加而降低，而绿色荧光强度增加，证实 CSA 孵育的细胞脂质严重过氧化物。此外，使用 CLSM 测量细胞凋亡标志物裂解的 caspase-3 的表达水平。结果显示，在有或没有激光照射处理的情况下，用 CSA 孵育的细胞中绿色荧光强度增加（图 4D），这意味着细胞中诱导了细胞凋亡。
基于可诱导溶酶体膜 LPO 的 ROS 的产生，使用 C11-BODIPY581/591 探针阐明 CSA 触发的 LPO，结果如图 4C 所示。结果显示，红色荧光强度随 CSA 浓度的增加而降低，而绿色荧光强度增加，证实 CSA 孵育的细胞脂质严重过氧化物。此外，使用 CLSM 测量细胞凋亡标志物裂解的 caspase-3 的表达水平。结果显示，在有或没有激光照射处理的情况下，用 CSA 孵育的细胞中绿色荧光强度增加（图 4D），这意味着细胞中诱导了细胞凋亡。
To further verify these results, western blotting analysis was utilized to assess the alterations in the expression levels of GPX4 and cleaved caspase-3 following a 48 h treatment with CSA in A549 cells under different conditions (Figure S24). It can be seen that a significant reduction in GPX4 expression and an apparent elevation of caspase-3 cleavage were observed. Furthermore, TrxR expression was reduced after cells were incubated with CSA (Figure S25). These observations indicated that the CSA depleted GSH and inhibited TrxR, subsequently leading to an increase in cellular ROS, inducing cell apoptosis. These findings provide further evidence of the potential of CSA in inducing cellular apoptosis.
为了进一步验证这些结果，利用蛋白质印迹分析来评估在不同条件下 A549 细胞中用 CSA 处理 48 小时后 GPX4 和裂解的 caspase-3 表达水平的变化（图 S24）。可以看出，观察到 GPX4 表达显著降低和 caspase-3 切割明显升高。此外，细胞与 CSA 一起孵育后，TrxR 表达降低（图 S25）。这些观察结果表明，CSA 耗尽 GSH 并抑制 TrxR，随后导致细胞 ROS 增加，诱导细胞凋亡。这些发现进一步证明了 CSA 在诱导细胞凋亡中的潜力。
为了进一步验证这些结果，利用蛋白质印迹分析来评估在不同条件下 A549 细胞中用 CSA 处理 48 小时后 GPX4 和裂解的 caspase-3 表达水平的变化（图 S24）。可以看出，观察到 GPX4 表达显著降低和 caspase-3 切割明显升高。此外，细胞与 CSA 一起孵育后，TrxR 表达降低（图 S25）。这些观察结果表明，CSA 耗尽 GSH 并抑制 TrxR，随后导致细胞 ROS 增加，诱导细胞凋亡。这些发现进一步证明了 CSA 在诱导细胞凋亡中的潜力。
In order to assess the lysosomal membrane integrity of A549 cells following incubation with CSA, an acridine orange (AO) staining method was utilized. As can be seen in Figure 4E, both green and yellow fluorescence were observed in untreated control cells. Upon incubation of A549 cells with CSA, the yellow fluorescence was greatly diminished, demonstrating that lysosomes were damaged, which may be due to CSA-induced ROS generation. Therefore, the results presented above suggested that laser irradiation of CSA-treated A549 cells could elicit cell apoptosis. The mechanisms implicated in CSA-mediated cancer cell killing involve GSH depletion and inhibition of TrxR and ROS-initiated LPO. These findings imply the potential of CSA as a potent therapeutic agent in cancer treatment.
为了评估 A549 细胞与 CSA 孵育后的溶酶体膜完整性，使用了吖啶橙 （AO） 染色方法。如图 4E 所示，在未处理的对照细胞中观察到绿色和黄色荧光。将 A549 细胞与 CSA 孵育后，黄色荧光大大减弱，表明溶酶体受损，这可能是由于 CSA 诱导的 ROS 生成。因此，上述结果表明，激光照射 CSA 处理的 A549 细胞可以引发细胞凋亡。CSA 介导的癌细胞杀伤机制涉及 GSH 耗竭和抑制 TrxR 和 ROS 启动的 LPO。这些发现意味着 CSA 作为癌症治疗中有效治疗剂的潜力。
为了评估 A549 细胞与 CSA 孵育后的溶酶体膜完整性，使用了吖啶橙 （AO） 染色方法。如图 4E 所示，在未处理的对照细胞中观察到绿色和黄色荧光。将 A549 细胞与 CSA 孵育后，黄色荧光大大减弱，表明溶酶体受损，这可能是由于 CSA 诱导的 ROS 生成。因此，上述结果表明，激光照射 CSA 处理的 A549 细胞可以引发细胞凋亡。CSA 介导的癌细胞杀伤机制涉及 GSH 耗竭和抑制 TrxR 和 ROS 启动的 LPO。这些发现意味着 CSA 作为癌症治疗中有效治疗剂的潜力。
2.6. In Vivo Antitumor Therapy of CSA
2.6. CSA 的体内抗肿瘤治疗
Inspired by the satisfactory comprehensive results of CSA in vitro, the synergistic therapeutic efficacy of CSA in vivo was evaluated using A549 tumor-bearing mice models. The A549 tumor-bearing mice were divided into five groups: PBS + L group, CS group, CS + L group, CSA group, and CSA + L group. The treatment groups underwent intratumoral injection of CSA (5 mg/kg), followed by irradiation with a 1064 nm laser. It can be seen that the temperature in the PBS + L group did not significantly change, whereas in the CSA + L group, there was a significant temperature increase, reaching 54 °C within 5 min (Figures 5A and S26), suggesting the excellent photothermal conversion capacity of CSA NPs in the tumor tissue.
受 CSA 体外令人满意的综合结果的启发，使用 A549 荷瘤小鼠模型评价了 CSA 在体内的协同治疗效果。将 A549 荷瘤小鼠分为 PBS + L 组、CS 组、CS + L 组、CSA 组和 CSA + L 组。治疗组瘤内注射 CSA （5 mg/kg），然后用 1064 nm 激光照射。可以看出，PBS + L 组的温度没有显着变化，而在 CSA + L 组中，温度显着升高，在 5 分钟内达到 54 °C（图 5A 和 S26），表明 CSA NPs 在肿瘤组织中具有优异的光热转换能力。
受 CSA 体外令人满意的综合结果的启发，使用 A549 荷瘤小鼠模型评价了 CSA 在体内的协同治疗效果。将 A549 荷瘤小鼠分为 PBS + L 组、CS 组、CS + L 组、CSA 组和 CSA + L 组。治疗组瘤内注射 CSA （5 mg/kg），然后用 1064 nm 激光照射。可以看出，PBS + L 组的温度没有显着变化，而在 CSA + L 组中，温度显着升高，在 5 分钟内达到 54 °C（图 5A 和 S26），表明 CSA NPs 在肿瘤组织中具有优异的光热转换能力。
Figure 5 图 5
Figure 5. In vivo therapeutic effect and metastasis inhibition of CSA. (A) Infrared thermal images at the tumor sites of mice. Changes in the relative body weight (B), tumor volume (C), and tumor weight (D) of mice with different treatments (n = 6). (E) Photographs of tumors dissected from each group of mice on the 14th day. (F) Micrographs of H & E stained and TUNEL stained tumor slices on the 14th day in different groups (scale bar: 250 μm). Error bars represent standard deviation for n = 5; P values were based on Student’s t-test: ****P < 0.0001, ***P < 0.001, **P < 0.01, and *P < 0.05.
图 5.CSA 的体内治疗效果和转移抑制。（A） 小鼠肿瘤部位的红外热图像。不同处理 （n = 6） 小鼠相对体重 （B） 、肿瘤体积 （C） 和肿瘤重量 （D） 的变化。（E） 第 14 天从每组小鼠解剖的肿瘤照片。（F） 不同组第 14 天 H & E 染色和 TUNEL 染色肿瘤切片的显微照片（比例尺：250 μm）。误差线表示 n = 5 的标准差;P 值基于学生的 t 检验：******P < 0.0001，***P < 0.001，**P < 0.01，*P < 0.05。
The weight of mouse, tumor volumes, and tumor weight of different groups were recorded every 2 days post irradiation during 14 days. It was found that within 14 days of the treatment, the body weight of all the treated mice showed no obvious change (Figure 5B), indicating excellent biocompatibility and no acute in vivo toxicity of CSA. Besides, negligible hemolysis of red blood cells was observed in the presence of CSA (Figure S27), suggesting its compatibility with blood. As presented in Figure 5C, the tumors of mice in the PBS + L, CS, and CSA groups showed rapid growth, showing minimal antitumor effects. In contrast, the tumors of mice in CS + L and CSA + L groups displayed effective tumor-restraint and gradual disappearance, implying the best synergistic effect of NIR-II photothermal and enhanced catalytic properties for antitumor therapy. After 14 days, the tumors and major organs were harvested. As displayed in Figure 5D,E, the weights of tumors from the dissected mice further confirmed the superior therapeutic effect of the CSA + L group, offering the same conclusion about the excellent tumor inhibition effect. In order to investigate the antitumor effect of CSA, the histological analysis for tumor sections harvested from each group of mice, including hematoxylin and eosin staining (H & E) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), was performed (Figure 5F). It can be seen that nearly no or litter dead cells were observed in the PBS + L, CS, and CS + L groups, while severe damage and necrosis presented in the CSA + L group in H & E staining, suggesting that photothermal-enhanced catalytic activity could significantly improve the therapeutic efficiency in tumor treatment. TUNEL staining revealed that compared to other groups, the tumor cell apoptosis increased in the CSA + L group. Taken together, these findings provide further evidence of the efficient antitumor effect of CSA for photothermal/catalytic synergistic therapy. Furthermore, to further assess the biosafety of CSA, H & E staining was performed to study the histological changes of major organs such as liver, spleen, lung, and kidney (Figure S28). No obvious signs of inflammation or tissue damage were observed in these main organs. In order to evaluate the in vivo biodistribution behavior of CSA in A549 tumor-bearing mice, in vivo fluorescence imaging and ICP-MS were performed. As shown in Figures S29 and S30, CSA could deposit at the site of the tumor tissues and then be cleared by the liver. All of these results suggested that CSA does not have any obvious side effects or toxicity, thus supporting the feasibility of using CSA as a smart agent for cancer therapy in vivo.
照射后 14 天内每 2 天记录小鼠体重、肿瘤体积和不同组的肿瘤重量。结果发现，在治疗后 14 天内，所有治疗小鼠的体重均无明显变化（图 5B），表明具有良好的生物相容性，并且没有 CSA 的急性体内毒性。此外，在 CSA 存在下观察到红细胞溶血可忽略不计（图 S27），表明它与血液相容。如图 5C 所示，PBS + L 、 CS 和 CSA 组小鼠的肿瘤表现出快速生长，显示出最小的抗肿瘤作用。相比之下，CS + L 和 CSA + L 组小鼠的肿瘤表现出有效的肿瘤抑制和逐渐消失，表明 NIR-II 光热和增强的抗肿瘤治疗催化作用最佳。14 天后，收获肿瘤和主要器官。如图 5D、E 所示，解剖小鼠的肿瘤重量进一步证实了 CSA + L 组的优越治疗效果，提供了关于优异肿瘤抑制效果的相同结论。为了研究CSA的抗肿瘤作用，对从每组小鼠身上收获的肿瘤切片进行了组织学分析，包括苏木精和伊红染色（H&E）和末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）（图5F）。可以看出，PBS + L、CS 和 CS + L 组几乎没有或观察到死细胞，而 CSA + L 组在 H & E 染色中呈现严重的损伤和坏死，表明光热增强的催化活性可以显着提高肿瘤治疗的治疗效果。 TUNEL 染色显示，与其他组相比，CSA + L 组肿瘤细胞凋亡增加。综上所述，这些发现进一步证明了 CSA 对光热/催化协同治疗的有效抗肿瘤作用。此外，为了进一步评估CSA的生物安全性，进行了H和E染色以研究肝、脾、肺和肾等主要器官的组织学变化（图S28）。在这些主要器官中未观察到明显的炎症或组织损伤迹象。为了评估 CSA 在 A549 荷瘤小鼠体内的生物分布行为，进行了体内荧光成像和 ICP-MS。如图 S29 和 S30 所示，CSA 可以沉积在肿瘤组织部位，然后被肝脏清除。所有这些结果表明，CSA 没有任何明显的副作用或毒性，从而支持了使用 CSA 作为体内癌症治疗的智能药物的可行性。
照射后 14 天内每 2 天记录小鼠体重、肿瘤体积和不同组的肿瘤重量。结果发现，在治疗后 14 天内，所有治疗小鼠的体重均无明显变化（图 5B），表明具有良好的生物相容性，并且没有 CSA 的急性体内毒性。此外，在 CSA 存在下观察到红细胞溶血可忽略不计（图 S27），表明它与血液相容。如图 5C 所示，PBS + L 、 CS 和 CSA 组小鼠的肿瘤表现出快速生长，显示出最小的抗肿瘤作用。相比之下，CS + L 和 CSA + L 组小鼠的肿瘤表现出有效的肿瘤抑制和逐渐消失，表明 NIR-II 光热和增强的抗肿瘤治疗催化作用最佳。14 天后，收获肿瘤和主要器官。如图 5D、E 所示，解剖小鼠的肿瘤重量进一步证实了 CSA + L 组的优越治疗效果，提供了关于优异肿瘤抑制效果的相同结论。为了研究CSA的抗肿瘤作用，对从每组小鼠身上收获的肿瘤切片进行了组织学分析，包括苏木精和伊红染色（H&E）和末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）（图5F）。可以看出，PBS + L、CS 和 CS + L 组几乎没有或观察到死细胞，而 CSA + L 组在 H & E 染色中呈现严重的损伤和坏死，表明光热增强的催化活性可以显着提高肿瘤治疗的治疗效果。 TUNEL 染色显示，与其他组相比，CSA + L 组肿瘤细胞凋亡增加。综上所述，这些发现进一步证明了 CSA 对光热/催化协同治疗的有效抗肿瘤作用。此外，为了进一步评估CSA的生物安全性，进行了H和E染色以研究肝、脾、肺和肾等主要器官的组织学变化（图S28）。在这些主要器官中未观察到明显的炎症或组织损伤迹象。为了评估 CSA 在 A549 荷瘤小鼠体内的生物分布行为，进行了体内荧光成像和 ICP-MS。如图 S29 和 S30 所示，CSA 可以沉积在肿瘤组织部位，然后被肝脏清除。所有这些结果表明，CSA 没有任何明显的副作用或毒性，从而支持了使用 CSA 作为体内癌症治疗的智能药物的可行性。
3. Conclusions 3. 结论
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In summary, a nanozyme platform (CSA) based on Ag-decorated CuSe hollow nanocubes was designed to interfere with cellular redox homeostasis and catalyze a cascade of intracellular biochemical reactions to produce ROS for synergistic cancer therapy of PTT/chemodynamic therapy/photoenhanced catalytic therapy. CSA shows the activity to deplete GSH, leading to GSH reduction, and inhibits the TrxR activity, disrupting redox homeostasis and increasing intracellular ROS levels. Due to the rapid Cu(II)/Cu(I) redox cycling, H2O2 cycling, and abundant catalytically active metal binding sites, CSA shows strong peroxidase-mimicking activity, releasing ROS including •OH, •O2–, and 1O2. Additionally, the SPR effects of Ag enable CSA to exhibit excellent optical adsorption under the NIR II window. The AgNPs can capture the electrons from the CS via the metal to metal charge transfer, reducing O2 to generate •O2–. Taking advantage of the high peroxidase-mimicking activity, excellent photothermal performance, GSH depletion, and inhibition of TrxR, this platform realized excellent tumor growth inhibition. Therefore, this work presents a new method for designing nanozymes as a ROS source for inducing cell apoptosis and targeting TrxR activity to disrupt cellular redox homeostasis, thereby offering an effective strategy in cancer therapy. Although this work is more an initial proof study, we believe that it lays the foundation for cancer therapy through disrupting cellular redox homeostasis to amplify ROS generation, greatly expanding the application of nanozymes in life science.
综上所述，基于 Ag 修饰的 CuSe 空心纳米立方体的纳米酶平台 （CSA） 旨在干扰细胞氧化还原稳态并催化细胞内生化反应的级联反应，以产生 ROS，用于 PTT/化学动力学疗法/光增强催化疗法的协同癌症治疗。CSA 显示出消耗 GSH 的活性，导致 GSH 减少，并抑制 TrxR 活性，破坏氧化还原稳态并增加细胞内 ROS 水平。由于快速的 Cu（II）/Cu（I） 氧化还原循环、H2O2 循环和丰富的催化活性金属结合位点，CSA 显示出很强的过氧化物酶模拟活性，释放出包括 •OH、•O2– 和 1O2 在内的 ROS。此外，Ag 的 SPR 效应使 CSA 能够在 NIR II 窗口下表现出优异的光学吸附。AgNP 可以通过金属到金属的电荷转移从 CS 捕获电子，还原 O2 以产生 •O2–。利用高过氧化物酶模拟活性、优异的光热性能、GSH 耗竭和 TrxR 抑制作用，该平台实现了优异的肿瘤生长抑制。因此，这项工作提出了一种将纳米酶设计为诱导细胞凋亡和靶向 TrxR 活性以破坏细胞氧化还原稳态的 ROS 来源的新方法，从而为癌症治疗提供有效的策略。虽然这项工作更多的是初步验证研究，但我们相信它通过破坏细胞氧化还原稳态以扩增 ROS 的产生，为癌症治疗奠定了基础，极大地扩展了纳米酶在生命科学中的应用。
综上所述，基于 Ag 修饰的 CuSe 空心纳米立方体的纳米酶平台 （CSA） 旨在干扰细胞氧化还原稳态并催化细胞内生化反应的级联反应，以产生 ROS，用于 PTT/化学动力学疗法/光增强催化疗法的协同癌症治疗。CSA 显示出消耗 GSH 的活性，导致 GSH 减少，并抑制 TrxR 活性，破坏氧化还原稳态并增加细胞内 ROS 水平。由于快速的 Cu（II）/Cu（I） 氧化还原循环、H2O2 循环和丰富的催化活性金属结合位点，CSA 显示出很强的过氧化物酶模拟活性，释放出包括 •OH、•O2– 和 1O2 在内的 ROS。此外，Ag 的 SPR 效应使 CSA 能够在 NIR II 窗口下表现出优异的光学吸附。AgNP 可以通过金属到金属的电荷转移从 CS 捕获电子，还原 O2 以产生 •O2–。利用高过氧化物酶模拟活性、优异的光热性能、GSH 耗竭和 TrxR 抑制作用，该平台实现了优异的肿瘤生长抑制。因此，这项工作提出了一种将纳米酶设计为诱导细胞凋亡和靶向 TrxR 活性以破坏细胞氧化还原稳态的 ROS 来源的新方法，从而为癌症治疗提供有效的策略。虽然这项工作更多的是初步验证研究，但我们相信它通过破坏细胞氧化还原稳态以扩增 ROS 的产生，为癌症治疗奠定了基础，极大地扩展了纳米酶在生命科学中的应用。
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The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsbiomaterials.4c00929.
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Additional experimental materials, methods, and characterization data for the preparation of CSA and CS and other in vitro and in vivo experimental data (PDF)
用于制备 CSA 和 CS 的其他实验材料、方法和表征数据以及其他体外和体内实验数据 （PDF）
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Author Information 作者信息
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- Pinghua ling - Laboratory of Functionalized Molecular Solids, Ministry of Education, Anhui Province Key Laboratory of Biomedical Materials and Chemical Measurement, College of Chemistry and Materials Science, Anhui Normal University, Wuhu 241002, China;
https://orcid.org/0000-0002-0289-8147;
凌平华 - 功能化分子固体教育部实验室，安徽师范大学化学与材料科学学院，安徽省生物医用材料与化学测量重点实验室，中国 241002; https://orcid.org/0000-0002-0289-8147;
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Acknowledgments 确认
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We gratefully acknowledge support from the National Natural Science Foundation of China (22074002 and 21705004), the University Scientific Research Plan of Anhui Province for funding (2023AH020030), the Doctoral Fund of Jining NO.1 People’s Hospital (2022-BS-004), and the Natural Science Foundation of Shandong Province (ZR2023QB151).
感谢国家自然科学基金（22074002和21705004）、安徽省高校科学研究计划（2023AH020030）、济宁市第一人民医院博士生基金（2022-BS-004）和山东省自然科学基金（ZR2023QB151）的支持。
References 引用
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This article references
57 other publications.
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- 1Halliwell, B. Reactive oxygen species in living systems: Source, biochemistry, and role in human disease. Am. J. Med. 1991, 91, S14– S22, DOI: 10.1016/0002-9343(91)90279-7Google Scholar 谷歌学术1https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK38Xitlartr0%253D&md5=f4e66294a9ca6b2decbc79fec993171dReactive oxygen species in living systems: source, biochemistry, and role in human diseaseHalliwell, BarryAmerican Journal of Medicine (1991), 91 (3C), 14S-22CODEN: AJMEAZ; ISSN:0002-9343.A review with 62 refs. Reactive oxygen species are constantly formed in the human body and removed by antioxidant defenses. An antioxidant is a substrate that, when present at low concns. compared to that of an oxidizable substrate, delays or prevents oxidn. of that substrate. Antioxidants can act by scavenging biol. important reactive oxygen species (O2-·, H2O2, ·OH, HOCl, ferryl, peroxyl, and alkoxyl) by preventing their formation, or by repairing the damage that they do. One problem with scavenging-type antioxidants is that secondary radicals derived from them can often themselves do biol. damage. These various principles are illustrated by considering several thiol compds.
1Halliwell， B. 生命系统中的活性氧：来源、生物化学和在人类疾病中的作用。美国医学杂志 1991， 91， S14– S22， DOI： 10.1016/0002-9343（91）90279-7内容谷歌学术1https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK38Xitlartr0%253D&md5=f4e66294a9ca6b2decbc79fec993171d 的更多生命系统中的活性氧：来源、生物化学和在人类疾病中的作用Halliwell， BarryAmerican Journal of Medicine （1991 年）、 91 （3C）、 14S-22 型科登： 阿吉米兹; 国际标准书号：0002-9343。一篇有 62 个参考文献的评论。 活性氧在人体内不断形成，并被抗氧化防御去除。 抗氧化剂是一种底物，当以低浓度存在时。与可氧化基材相比，可延迟或防止氧化。的。 抗氧化剂可以通过清除生物。重要的活性氧（O2-·、H2O2、·OH、HOCl、铁基、过氧基和烷氧基）通过阻止它们的形成或修复它们造成的损害。 清除型抗氧化剂的一个问题是，从它们衍生的次级自由基本身通常可以造成生物损伤。 通过考虑几种硫醇组合来说明这些不同的原理。 - 2Yang, B.; Chen, Y.; Shi, J. Reactive Oxygen Species (ROS)-Based Nanomedicine. Chem. Rev. 2019, 119, 4881– 4985, DOI: 10.1021/acs.chemrev.8b00626Google Scholar 谷歌学术2https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXnt1Sht7c%253D&md5=f2580253fcf77f9672a4fcb1713e3f59Reactive Oxygen Species (ROS)-Based NanomedicineYang, Bowen; Chen, Yu; Shi, JianlinChemical Reviews (Washington, DC, United States) (2019), 119 (8), 4881-4985CODEN: CHREAY; ISSN:0009-2665. (American Chemical Society)A review. Reactive oxygen species (ROS) play an essential role in regulating various physiol. functions of living organisms. The intrinsic biochem. properties of ROS, which underlie the mechanisms necessary for the growth, fitness, or aging of living organisms, have been driving researchers to take full advantage of these active chem. species for contributing to medical advances. Thanks to the remarkable advances in nanotechnol., great varieties of nanomaterials with unique ROS-regulating properties have been explored to guide the temporospatial dynamic behaviors of ROS in biol. milieu, which contributes to the emergence of a new-generation therapeutic methodol., i.e., nanomaterial-guided in vivo ROS evolution for therapy. The interdependent relationship between ROS and their corresponding chem., biol., and nanotherapy leads us to propose the concept of "ROS science", which is believed to be an emerging scientific discipline that studies the chem. mechanisms, biol. effects, and nanotherapeutic applications of ROS. In this review, state-of-art studies concerning recent progresses on ROS-based nanotherapies have been summarized in detail, with an emphasis on underlying material chem. of nanomaterials by which ROS are generated or scavenged for improved therapeutic outcomes. Furthermore, key scientific issues in the evolution of ROS-based cross-disciplinary fields have also been discussed, aiming to unlock the innate powers of ROS for optimized therapeutic efficacies. We expect that our demonstration on this evolving field will be beneficial to the further development of ROS-based fundamental researches and clin. applications.
2杨 B.;陈 Y.;石 J. 基于活性氧 （ROS） 的纳米医学。化学修订版 2019， 119， 4881– 4985， DOI： 10.1021/acs.chemrev.8b00626谷歌学术2内容？origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXnt1Sht7c%253D&md5=f2580253fcf77f9672a4fcb1713e3f59基于活性氧 （ROS） 的纳米医学Yang， Bowen;陈宇;Shi， JianlinChemical Reviews （美国 华盛顿特区） （2019 年）， 票价：119 （8）、 4881-4985科登： 克雷; 国际标准书号：0009-2665。 （美国化学学会）评论。 活性氧 （ROS） 在调节生物体的各种生理功能中起着至关重要的作用。 内在的生物化学。ROS 的特性是生物体生长、适应或衰老所必需的机制的基础，一直推动研究人员充分利用这些活性化学物种为医学进步做出贡献。 由于纳米技术的显着进步，已经探索了大量具有独特 ROS 调节特性的纳米材料，以指导 ROS 在生物环境中的时空动力学行为，这有助于新一代治疗方法的出现，即纳米材料引导的体内 ROS 进化用于治疗。 ROS 与其相应的化学、生物和纳米疗法之间的相互依存关系促使我们提出了“ROS 科学”的概念，它被认为是一门新兴的科学学科，研究 ROS 的化学机制、生物学效应和纳米治疗应用。 在本综述中，详细总结了有关基于 ROS 的纳米疗法最新进展的最新研究，重点是纳米材料的基础材料化学。通过这些材料产生或清除 ROS 以改善治疗结果。 此外，还讨论了基于 ROS 的跨学科领域发展中的关键科学问题，旨在释放 ROS 的内在力量以优化治疗效果。 我们预计，我们在这个不断发展的领域的演示将有利于基于 ROS 的基础研究和临床的进一步发展。应用。 - 3Schumacker, P. T. Reactive oxygen species in cancer cells: Live by the sword, die by the sword. Cancer Cell 2006, 10, 175– 176, DOI: 10.1016/j.ccr.2006.08.015Google Scholar 谷歌学术3https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28XhtVSlu73M&md5=aa7c8ed4524ce0392d478c53090925d1Reactive oxygen species in cancer cells: live by the sword, die by the swordSchumacker, Paul T.Cancer Cell (2006), 10 (3), 175-176CODEN: CCAECI; ISSN:1535-6108. (Cell Press)A review. Reactive oxygen species and tumor biol. are intertwined in a complex web, making it difficult to understand which came first, whether oxidants are required for tumor cell growth, and whether oxidant stress can be exploited therapeutically. Evidence suggests that transformed cells use ROS signals to drive proliferation and other events required for tumor progression. This confers a state of increased basal oxidative stress, making them vulnerable to chemotherapeutic agents that further augment ROS generation or that weaken antioxidant defenses of the cell. In this respect, it appears that tumor cells may die by the same systems they require.
3Schumacker， PT 癌细胞中的活性氧：活在刀剑下，死于刀剑。癌细胞 2006， 10， 175– 176， DOI： 10.1016/j.ccr.2006.08.015内容Google Scholar3癌细胞中的活性氧：活在刀下，死于刀剑舒马克，保罗 T.癌细胞 （2006 年）、 10 （3）、 175-176 元科登： CCAECI; 国际标准书号：1535-6108。 （细胞出版社）评论。 活性氧和肿瘤生物学交织在一个复杂的网络中，因此很难理解哪个先出现，肿瘤细胞生长是否需要氧化剂，以及氧化剂应激是否可以用于治疗。 有证据表明，转化的细胞使用 ROS 信号来驱动增殖和肿瘤进展所需的其他事件。 这赋予了一种基础氧化应激增加的状态，使它们容易受到化疗剂的影响，这些化疗剂会进一步增加 ROS 的产生或削弱细胞的抗氧化防御。 在这方面，肿瘤细胞似乎可能会因它们需要的相同系统而死亡。 - 4Trachootham, D.; Alexandre, J.; Huang, P. Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach?. Nat. Rev. Drug Discovery 2009, 8, 579– 591, DOI: 10.1038/nrd2803Google Scholar 谷歌学术4https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXmsFWqsLk%253D&md5=d50931b8de8bcab62d376becc768a71cTargeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach?Trachootham, Dunyaporn; Alexandre, Jerome; Huang, PengNature Reviews Drug Discovery (2009), 8 (7), 579-591CODEN: NRDDAG; ISSN:1474-1776. (Nature Publishing Group)A review. Increased generation of reactive oxygen species (ROS) and an altered redox status have long been obsd. in cancer cells, and recent studies suggest that this biochem. property of cancer cells can be exploited for therapeutic benefits. Cancer cells in advanced stage tumors frequently exhibit multiple genetic alterations and high oxidative stress, suggesting that it might be possible to preferentially eliminate these cells by pharmacol. ROS insults. However, the upregulation of antioxidant capacity in adaptation to intrinsic oxidative stress in cancer cells can confer drug resistance. Abrogation of such drug-resistant mechanisms by redox modulation could have significant therapeutic implications. We argue that modulating the unique redox regulatory mechanisms of cancer cells might be an effective strategy to eliminate these cells.
4特拉楚瑟姆，D.;亚历山大，J.;黄 P. 通过 ROS 介导的机制靶向癌细胞：一种激进的治疗方法？Nat. Rev. 药物发现 2009， 8， 579– 591， DOI： 10.1038/nrd2803内容Google Scholar4https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXmsFWqsLk%253D&md5=d50931b8de8bcab62d376becc768a71c 的更多通过 ROS 介导的机制靶向癌细胞：一种激进的治疗方法？Trachootham，Dunyaporn;亚历山大，杰罗姆;Huang， PengNature Reviews 药物发现 （2009 年）、 8 （7）、 579-591 号科登： NRDDAG 的; 国际标准书号：1474-1776。 （自然出版集团）评论。 长期以来，活性氧 （ROS） 的产生增加和氧化还原状态的改变一直是人们关注的焦点。在癌细胞中，最近的研究表明，这种生化。癌细胞的特性可以被利用以获得治疗益处。 晚期肿瘤中的癌细胞经常表现出多种基因改变和高氧化应激，这表明有可能通过药物优先消除这些细胞。ROS 侮辱。 然而，癌细胞适应内在氧化应激的抗氧化能力上调会赋予耐药性。 通过氧化还原调节消除这种耐药机制可能具有重要的治疗意义。 我们认为，调节癌细胞独特的氧化还原调节机制可能是消除这些细胞的有效策略。 - 5Nathan, C.; Cunningham-Bussel, A. Beyond oxidative stress: an immunologist’s guide to reactive oxygen species. Nat. Rev. Immunol. 2013, 13, 349– 361, DOI: 10.1038/nri3423Google Scholar 谷歌学术5https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXmsFagtLY%253D&md5=bff72ccca0ea4a4065b02812ec1f03e4Beyond oxidative stress: an immunologist's guide to reactive oxygen speciesNathan, Carl; Cunningham-Bussel, AmyNature Reviews Immunology (2013), 13 (5), 349-361CODEN: NRIABX; ISSN:1474-1733. (Nature Publishing Group)A review. Reactive oxygen species (ROS) react preferentially with certain atoms to modulate functions ranging from cell homeostasis to cell death. Mol. actions include both inhibition and activation of proteins, mutagenesis of DNA and activation of gene transcription. Cellular actions include promotion or suppression of inflammation, immunity and carcinogenesis. ROS help the host to compete against microorganisms and are also involved in intermicrobial competition. ROS chem. and their pleiotropy make them difficult to localize, to quantify and to manipulate - challenges we must overcome to translate ROS biol. into medical advances.
5内森，C.;坎宁安-巴塞尔 超越氧化应激：免疫学家的活性氧指南。Nat. Rev. 免疫学。 2013， 13， 349– 361， DOI： 10.1038/nri3423内容Google Scholar5超越氧化应激：活性氧免疫学家指南Nathan， Carl;Cunningham-Bussel， AmyNature 评论免疫学 （2013 年）、 13 （5）、 349-361 元科登： NRIABX的; 国际标准书号：1474-1733。 （自然出版集团）评论。 活性氧 （ROS） 优先与某些原子反应，以调节从细胞稳态到细胞死亡的功能。 分子作用包括抑制和激活蛋白质、DNA 诱变和激活基因转录。 细胞作用包括促进或抑制炎症、免疫和致癌作用。 ROS 帮助宿主与微生物竞争，也参与微生物间竞争。 ROS 化学及其多效性使它们难以定位、量化和操纵 - 我们必须克服这些挑战才能将 ROS 生物转化为医学进步。 - 6Fraisl, P.; Aragonés, J.; Carmeliet, P. Inhibition of oxygen sensors as a therapeutic strategy for ischaemic and inflammatory disease. Nat. Rev. Drug Discovery 2009, 8, 139– 152, DOI: 10.1038/nrd2761Google Scholar 谷歌学术6https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXpsVCjtQ%253D%253D&md5=37f75a6f71c3dac2bb818ee19378dd8cInhibition of oxygen sensors as a therapeutic strategy for ischaemic and inflammatory diseaseFraisl, Peter; Aragones, Julian; Carmeliet, PeterNature Reviews Drug Discovery (2009), 8 (2), 139-152CODEN: NRDDAG; ISSN:1474-1776. (Nature Publishing Group)A review. Cells in the human body need oxygen to function and survive, and severe deprivation of oxygen, as occurs in ischemic heart disease and stroke, is a major cause of mortality. Nevertheless, other organisms, such as the fossorial mole rat or diving seals, have acquired the ability to survive in conditions of limited oxygen supply. Hypoxia tolerance also allows the heart to survive chronic oxygen shortage, and ischemic preconditioning protects tissues against lethal hypoxia. The recent discovery of a new family of oxygen sensors, including prolyl hydroxylase domain-contg. proteins 1-3 (PHD1-3), has yielded exciting novel insights into how cells sense oxygen and keep oxygen supply and consumption in balance. Advances in understanding of the role of these oxygen sensors in hypoxia tolerance, ischemic preconditioning and inflammation are creating new opportunities for pharmacol. interventions for ischemic and inflammatory diseases.
6弗莱尔，P.;阿拉贡内斯，J.;卡梅利特，P. 抑制氧传感器作为缺血性和炎症性疾病的治疗策略。Nat. Rev. Drug Discovery 2009， 8， 139– 152， DOI： 10.1038/nrd2761内容谷歌学术6抑制氧传感器作为缺血性和炎症性疾病的治疗策略Fraisl， Peter;朱利安·阿拉贡内斯;Carmeliet， PeterNature 评论药物发现 （2009 年）、 8 （2）， 139-152 元科登： NRDDAG 的; 国际标准书号：1474-1776。 （自然出版集团）评论。 人体细胞需要氧气才能运作和生存，而严重缺氧（如缺血性心脏病和中风）是导致死亡的主要原因。 然而，其他生物，如化石鼹鼠或潜水海豹，已经获得了在氧气供应有限的条件下生存的能力。 缺氧耐受性还使心脏能够在慢性缺氧的情况下存活，缺血预处理可保护组织免受致命的缺氧。 最近发现了一个新的氧传感器系列，包括脯氨酰羟化酶结构域-contg。蛋白 1-3 （PHD1-3） 对细胞如何感知氧气并保持氧气供应和消耗平衡产生了令人兴奋的新见解。 对这些氧传感器在缺氧耐受性、缺血预处理和炎症中的作用的理解取得的进展正在为药理学创造新的机会。缺血性和炎症性疾病的干预措施。 - 7Yu, L.; Xu, Y.; Pu, Z.; Kang, H.; Li, M.; Sessler, J. L.; Kim, J. S. Photocatalytic Superoxide Radical Generator that Induces Pyroptosis in Cancer Cells. J. Am. Chem. Soc. 2022, 144, 11326– 11337, DOI: 10.1021/jacs.2c03256Google Scholar 谷歌学术7https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XhsFanu7fP&md5=21e3b0a58e62e1b4ab44ed9e1824889cPhotocatalytic Superoxide Radical Generator that Induces Pyroptosis in Cancer CellsYu, Le; Xu, Yunjie; Pu, Zhongji; Kang, Heemin; Li, Mingle; Sessler, Jonathan L.; Kim, Jong SeungJournal of the American Chemical Society (2022), 144 (25), 11326-11337CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Pyroptosis, a newly characterized form of immunogenic cell death, is attracting increasing attention as a promising approach to cancer immunotherapy. However, biocompatible strategies to activate pyroptosis remain rare. Here, we show that a photocatalytic superoxide radical (O2-•) generator, NI-TA, triggers pyroptosis in cancer cells. NI-TA was designed to take advantage of an intramol. triplet-ground state splitting energy modulation approach. Detailed studies revealed that the pyroptosis triggered by NI-TA under conditions of photoexcitation proceeds through a caspase-3/gasdermin E (GSDME) pathway rather than via canonical processes involving caspase-1/gasdermin-D (GSDMD). NI-TA was found to function via a partial-O2-recycling mode of action and to trigger cell pyroptosis and provide for effective cancer cell ablation even under conditions of hypoxia (≤2% O2). In the case of T47D 3D multicellular spheroids, good antitumor efficiency and stemness inhibition are achieved. This work highlights how photocatalytic chem. may be leveraged to develop effective pyroptosis-inducing agents.
7余 L.;徐 Y.;蒲 Z.;康，H.;李 M.;塞斯勒，JL;金 J. S. 光催化超氧自由基发生器，在癌细胞中诱导焦亡。J. Am. Chem. Soc. 2022， 144， 11326– 11337， DOI： 10.1021/jacs.2c03256内容谷歌学术7在癌细胞中诱导焦亡的光催化超氧自由基发生器Yu， Le;徐云杰;蒲忠吉;康，海敏;李明乐;塞斯勒，乔纳森 L.;Kim， Jong Seung美国化学会杂志 （2022 年）， 144 元 （25）、 11326 - 11337科登： JACSAT公司; 国际标准书号：0002-7863。 （美国化学学会）焦亡是一种新表征的免疫原性细胞死亡形式，作为一种很有前途的癌症免疫治疗方法，越来越受到关注。 然而，激活细胞焦亡的生物相容性策略仍然很少见。 在这里，我们展示了光催化超氧自由基 （O2-•） 发生器 NI-TA 会触发癌细胞焦亡。 NI-TA 旨在利用 intramol.三重态-地态分裂能量调制方法。 详细的研究表明，在光激发条件下，NI-TA 触发的焦亡通过 caspase-3/gasdermin E （GSDME） 途径进行，而不是通过涉及 caspase-1/gasdermin-D （GSDMD） 的经典过程进行。 发现 NI-TA 通过部分 O2 循环作用模式发挥作用，即使在缺氧 （≤2% O2） 条件下也能触发细胞焦亡并提供有效的癌细胞消融。 在 T47D 3D 多细胞球体的情况下，实现了良好的抗肿瘤效率和干性抑制。 这项工作强调了如何利用光催化化学来开发有效的焦亡诱导剂。 - 8Wang, Z.; Wei, M.; Liu, Q.; Lu, X.; Zhou, J.; Wang, J. Oxygen-defective zinc oxide nanoparticles as highly efficient and safe sonosensitizers for cancer therapy. Chem. Commun. 2023, 59, 10968– 10971, DOI: 10.1039/D3CC02486E
8王 Z.;魏，M.;刘 Q.;卢 X.;周，J.;王 J. 缺氧氧化锌纳米颗粒作为癌症治疗的高效和安全的声敏剂。化学公报。 2023， 59， 10968– 10971， DOI： 10.1039/D3CC02486EGoogle Scholar此参考文献没有相应的记录。 - 9Wang, Y.; Tang, Q.; Wu, R.; Sun, S.; Zhang, J.; Chen, J.; Gong, M.; Chen, C.; Liang, X. Ultrasound-Triggered Piezocatalysis for Selectively Controlled NO Gas and Chemodrug Release to Enhance Drug Penetration in Pancreatic Cancer. ACS Nano 2023, 17, 3557– 3573, DOI: 10.1021/acsnano.2c09948Google Scholar 谷歌学术9https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXivFWltL8%253D&md5=685ba2078bacec5a050551bc42116c5bUltrasound-Triggered Piezocatalysis for Selectively Controlled NO Gas and Chemodrug Release to Enhance Drug Penetration in Pancreatic CancerWang, Yuan; Tang, Qingshuang; Wu, Ruiqi; Sun, Suhui; Zhang, Jinxia; Chen, Jing; Gong, Ming; Chen, Chaoyi; Liang, XiaolongACS Nano (2023), 17 (4), 3557-3573CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Nitric oxide (NO) is drawing widespread attention in treating pancreatic ductal adenocarcinoma (PDAC) as a safe and therapeutically efficient technique through modulating the dense fibrotic stroma in the tumor microenvironment to enhance drug penetration. Considerable NO nanogenerators and NO releasing mols. have been developed to shield the systemic toxicity caused by free diffusion of NO gas. However, on-demand controlled release of NO and chemotherapy drugs at tumor sites remains a problem limited by the complex and dynamic tumor microenvironment. Herein, we present an ultrasound-responsive nanoprodrug of CPT-t-R-PEG2000@BaTiO3 (CRB) which encapsulates piezoelec. nanomaterials barium titanate nanoparticle (BaTiO3) with amphiphilic prodrug mols. that consisted of thioketal bond (t) linked chemotherapy drug camptothecin (CPT) and NO-donor L-arginine (R). Based on ultrasound-triggered piezocatalysis, BaTiO3 can continuously generate ROS in the hypoxic tumor environment, which induces a cascade of reaction processes to break the thioketal bond to release CPT and oxidize R to release NO, simultaneously delivering CPT and NO to the tumor site. It is revealed that CRB shows a uniform size distribution, prolonged blood circulation time, and excellent tumor targeting ability. Moreover, controlled release of CPT and NO were obsd. both in vitro and in vivo under the stimulation of ultrasound, which is beneficial to the depletion of dense stroma and subsequently enhanced delivery and efficacy of CPT. Taken together, CRB significantly increased the antitumor efficacy against highly malignant Panc02 tumors in mice through inhibiting chemoresistance, representing a feasible approach for targeted therapies against Panc02 and other PDAC.
9王 Y.;唐 Q.;吴，R.;Sun， S.;张 J.;陈 J.;龚，M.;陈 C.;梁 X. 超声触发的压电催化，用于选择性控制 NO 气体和化疗药物释放，以增强药物在胰腺癌中的渗透性。ACS Nano 2023， 17， 3557– 3573， DOI： 10.1021/acsnano.2c09948Google Scholar9？origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXivFWltL8%253D&md5=685ba2078bacec5a050551bc42116c5b选择性控制 NO 气体和化学药物释放的超声触发压电催化作用以增强胰腺癌中的药物渗透Wang， Yuan;唐庆双;吴瑞琪;孙苏慧;张金霞;陈静;龚明;陈朝毅;梁小龙ACS Nano （2023 年）， 17 （4）、 3557-3573科登： ANCAC3; 国际标准书号：1936-0851。 （美国化学学会）一氧化氮 （NO） 在治疗胰腺导管腺癌 （PDAC） 方面受到广泛关注，它是一种安全且治疗有效的技术，通过调节肿瘤微环境中致密的纤维化基质以增强药物渗透。 相当多的 NO 纳米发生器和 NO 释放 mols。已被开发用于保护 NO 气体自由扩散引起的全身毒性。 然而，NO 和化疗药物在肿瘤部位的按需控制释放仍然是一个受复杂和动态肿瘤微环境限制的问题。 在此，我们提出了一种封装压电的 CPT-t-R-PEG2000@BaTiO3 （CRB） 的超声反应性纳米前药。纳米材料钛酸钡纳米颗粒 （BaTiO3） 与两亲性前药 mols。该药物包括硫硫克醛键 （t） 连接的化疗药物喜树碱 （CPT） 和 NO 供体 L-精氨酸 （R）。 基于超声触发的压电催化，BaTiO3 可以在缺氧肿瘤环境中持续产生 ROS，诱导一连串的反应过程打破硫菌醛键释放 CPT，氧化 R 释放 NO，同时将 CPT 和 NO 输送到肿瘤部位。 结果表明，CRB 表现出均匀的尺寸分布、延长的血液循环时间和出色的肿瘤靶向能力。 此外，CPT 和 NO 的控释是 obsd。在超声刺激下的体外和体内，有利于去除致密基质，从而增强 CPT 的递送和疗效。 综上所述，CRB 通过抑制化疗耐药性显著提高了小鼠对高度恶性 Panc02 肿瘤的抗肿瘤疗效，代表了针对 Panc02 和其他 PDAC 的靶向治疗的可行方法。 - 10Du, Z.; Wang, X.; Zhang, X.; Gu, Z.; Fu, X.; Gan, S.; Fu, T.; Xie, S.; Tan, W. X-Ray-triggered Carbon Monoxide and Manganese Dioxide Generation based on Scintillating Nanoparticles for Cascade Cancer Radiosensitization. Angew. Chem., Int. Ed. 2023, 62, e202302525 DOI: 10.1002/anie.202302525
10杜，Z.;王 X.;张 X.;顾 Z.;Fu， X.;甘，S.;傅 T.;谢 S.;谭 W. 基于闪烁纳米粒子的 X 射线触发的一氧化碳和二氧化锰生成，用于级联癌症放射增敏。Angew. Chem.， 国际教育 2023， 62， e202302525 DOI： 10.1002/anie.202302525谷歌学术此参考没有相应的记录。 - 11Zhang, R.; Ma, Q.; Hu, G.; Wang, L. Acid-Triggered H2O2 Self-Supplying Nanoplatform for 19F-MRI with Enhanced Chemo-Chemodynamic Therapy. Anal. Chem. 2022, 94, 3727– 3734, DOI: 10.1021/acs.analchem.2c00023Google Scholar 谷歌学术11https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XktVKhu7s%253D&md5=52076fd08320b4bf0ae541506b392cdbAcid-Triggered H2O2 Self-Supplying Nanoplatform for 19F-MRI with Enhanced Chemo-Chemodynamic TherapyZhang, Ruijuan; Ma, Qian; Hu, Gaofei; Wang, LeyuAnalytical Chemistry (Washington, DC, United States) (2022), 94 (8), 3727-3734CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)The real-time tracking and efficacy evaluation of therapeutic nanoplatforms esp. in deep-tissues is of great importance but faces challenges. Meanwhile, chemodynamic therapy (CDT), relying on Fenton reaction by converting H2O2 into toxic hydroxyl radicals (.OH), has drawn wide interests in the fabrication of nanozymes for tumor therapy, while endogenous H2O2 is usually insufficient for effective CDT. Here, we report the pH-responsive multifunctional nanoplatforms consisting of copper peroxide (CP) nanoparticles, paclitaxel (PTX) and perfluoro-15-crown-5-ether (PFCE), for 19F magnetic resonance imaging guided and enhanced chemo-chemodynamic synergetic therapy with self-supplied H2O2 stemmed from the decompn. of CP nanoparticles under acid conditions in tumor. The decompn. of CP nanoparticles further promotes the release of PTX for enhanced chemotherapy. Both in vitro and in vivo results indicate that the efficient generation of .OH and drug release effectively inhibits tumor growth. Furthermore, 19F MRI signal can clearly track the fate of nanoplatforms in tumor and guide tumor treatment. This work provides a promising strategy for the rational design and construction of multifunctional nanoplatforms for imaging-guided synergistic therapy of deep seated tumor.
11张 R.;马，Q.;胡 G.;王 L. 酸触发的 H2O2 自供给纳米平台，用于 19F-MRI 和增强的化学化学动力学治疗。Anal. 化学。 2022， 94， 3727– 3734， DOI： 10.1021/acs.analchem.2c00023内容谷歌学术11用于增强化学-化学动力学疗法的 19F-MRI 酸触发 H2O2 自供纳米平台张瑞娟;马，钱;胡高飞;Wang， LeyuAnalytical Chemistry （美国 华盛顿特区） （2022 年）， 94 （8）、 3727-3734科登： 安查姆; 国际标准书号：0003-2700。 （美国化学学会）治疗性纳米平台的实时跟踪和疗效评估，尤其是在深层组织中，非常重要，但也面临挑战。 同时，化学动力学疗法 （CDT） 依靠芬顿反应将 H 2 O 2 转化为有毒的羟基自由基 （.OH） 在制造用于肿瘤治疗的纳米酶方面引起了广泛的兴趣，而内源性 H 2 O 2 通常不足以进行有效的 CDT。 在这里，我们报道了由过氧化铜 （CP） 纳米颗粒、紫杉醇 （PTX） 和全氟-15-冠-5-醚 （PFCE） 组成的 pH 响应性多功能纳米平台，用于 19F 磁共振成像引导和增强的化学-化学动力学协同疗法，使用来自成分的自供 H 2 O 2 。肿瘤酸性条件下的 CP 纳米颗粒。 被淘汰的。的 CP 纳米颗粒进一步促进 PTX 的释放以增强化疗。 体外和体内结果表明，.OH 和药物释放可有效抑制肿瘤生长。 此外，19F MRI 信号可以清楚地追踪纳米平台在肿瘤中的命运并指导肿瘤治疗。 这项工作为合理设计和构建用于成像引导协同治疗深部肿瘤的多功能纳米平台提供了一种有前途的策略。 - 12Zhang, Y.; Zhang, Q.; Wang, F.; Li, M.; Shi, X.; Li, J. Activatable Semiconducting Polymer Nanoinducers Amplify Oxidative Damage via Sono-Ferroptosis for Synergistic Therapy of Bone Metastasis. Nano Lett. 2023, 23, 7699– 7708, DOI: 10.1021/acs.nanolett.3c02414Google Scholar 谷歌学术12https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXhs1Gqu7%252FE&md5=638377aa513934f506dc4b2ae3a2c2bcActivatable Semiconducting Polymer Nanoinducers Amplify Oxidative Damage via Sono-Ferroptosis for Synergistic Therapy of Bone MetastasisZhang, Yijing; Zhang, Qin; Wang, Fengshuo; Li, Meng; Shi, Xiangyang; Li, JingchaoNano Letters (2023), 23 (16), 7699-7708CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)Bone metastases are secondary malignant tumors that commonly occur after the spread of advanced cancer cells. We herein report the activatable semiconducting polymer nanoinducers (ASPNFP) that can amplify oxidative damage via sono-ferroptosis for bone metastasis treatment. ASPNFP are constructed by encapsulating plasma amine oxidase-based semiconducting polymer nanoparticles (SPNP) and Fe3O4 nanoparticles into singlet oxygen (1O2)-responsive nanocarriers. ASPNFP generate 1O2 under ultrasound (US) irradn. via a sonodynamic effect to destroy the stability of 1O2-responsive nanocarriers, allowing US-triggered releases of SPNP and Fe3O4 nanoparticles. SPNP decomp. polyamines in tumor cells to produce acrolein and hydrogen peroxide (H2O2), in which H2O2 promotes Fenton reaction mediated by Fe3O4 nanoparticles for inducing enhanced ferroptosis and generation of hydroxyl radicals (.OH). The generated acrolein, 1O2, and .OH can simultaneously amplify the oxidative damage. ASPNFP thus mediate an amplified sono-ferroptosis effect to inhibit the growth of bone metastasis and restrict tumor metastasis.
12张 Y.;张 Q.;王 F.;李 M.;石 X.;李杰 可激活的半导体聚合物纳米诱导剂通过声铁死亡放大氧化损伤，以协同治疗骨转移。纳米莱特。 2023， 23， 7699– 7708， DOI： 10.1021/acs.nanolett.3c02414内容谷歌学术搜索12可激活半导体聚合物纳米诱导剂通过声铁死亡放大氧化损伤，协同治疗骨转移张毅静;张琴;王凤硕;李孟;石向阳;李晶超纳米字母 （2023 年）， 23 （16）、 7699-7708科登： NALEFD的; 国际标准书号：1530-6984。 （美国化学学会）骨转移是继发性恶性肿瘤，通常发生在晚期癌细胞扩散后。 我们在此报道了可激活的半导体聚合物纳米诱导剂 （ASPNFP），它可以通过声铁死亡放大氧化损伤，用于治疗骨转移。 ASPNFP 是通过将基于等离子胺氧化酶的半导体聚合物纳米颗粒 （SPNP） 和 Fe3O4 纳米颗粒封装到单线态氧 （1O2） 响应性纳米载体中来构建的。 ASPNFP 在超声 （US） irradn 下生成 1O2。通过声动力学效应破坏 1O2 响应纳米载体的稳定性，允许 US 触发的 SPNP 和 Fe3O4 纳米颗粒的释放。 SPNP 分解。肿瘤细胞中的多胺产生丙烯醛和过氧化氢 （H2O2），其中 H2O2 促进 Fe3O4 纳米颗粒介导的芬顿反应，以诱导增强的铁死亡和羟基自由基的产生 （.OH）。 生成的丙烯醛 1O2 和 .OH 可以同时放大氧化损伤。 因此，ASPNFP 介导扩增的声铁死亡效应，以抑制骨转移的生长并限制肿瘤转移。 - 13Zhao, B.; Ma, Z.; Ding, S.; Cao, Y.; Du, J.; Zeng, L.; Hu, Y.; Zhou, J.; Zhang, X.; Bian, X. w.; Tian, G. Catalytic MnWO4 Nanorods for Chemodynamic Therapy Synergized Radiotherapy of Triple Negative Breast Cancer. Adv. Funct. Mater. 2023, 33, 2306328, DOI: 10.1002/adfm.202306328Google Scholar 谷歌学术13https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXhsVKltbfL&md5=881fa424ae7244d6187de7d6afbb5d5dCatalytic MnWO4 Nanorods for Chemodynamic Therapy Synergized Radiotherapy of Triple Negative Breast CancerZhao, Bin; Ma, Zhili; Ding, Shuaishuai; Cao, Yuhua; Du, Jiangfeng; Zeng, Lijuan; Hu, Yunping; Zhou, Jingrong; Zhang, Xiao; Bian, Xiu-wu; Tian, GanAdvanced Functional Materials (2023), 33 (47), 2306328CODEN: AFMDC6; ISSN:1616-301X. (Wiley-VCH Verlag GmbH & Co. KGaA)Nanomedicine-based synergy of chemodynamic therapy (CDT) and radiotherapy (RT) modulated by tumor microenvironment enables rapid tumor ablation, which holds great hope for the refractory and recurrent cancers, such as triple neg. breast cancer (TNBC). The clin. translation of hafnium oxide (HfO2), com. named as NBTXR3, has aroused new research focus on single-component inorg. nanomedicines as clin. candidates. Herein, the single-component MnWO4 is first reported as a new kind of Fenton-like agent yet radiosensitizer for TNBC treatment undergoing the synergistic CDT/RT mechanism. MnWO4 nanorods are synthesized via a simple one-pot hydrothermal method and then undergo a layer-by-layer PEGylation to obtain bioavailable MnWO4-PEG (MWP). MWP-based Fenton-like reaction efficacy depends on reaction time, temps., pH values, and MWP concns. Mn-triggered chemodynamic effect delays RT-induced DNA damage repair and sorts cell cycles distribution toward radiosensitive phases, while W-mediated radiosensitization improves the tumoral H2O2 overexpression to enhance CDT, remarkably amplifying of the intracellular oxidative stress to boost 4T1 cell apoptosis. In vitro and in vivo evaluations further demonstrate the effectiveness and biosafety of MWP-based synergistic therapy. Considering the potential magnetic resonance and computed tomog. imaging capabilities, MWP can be expected as an intelligent cancer theranostics for imaging-guided cancer therapy in clinic in the future.
13赵 B.;马，Z.;丁 S.;曹 Y.;杜 J.;曾， L.;胡 Y.;周，J.;张 X.;Bian， X. w.;田 G. 催化 MnWO4 纳米棒用于三阴性乳腺癌的化学动力学治疗协同放疗。Adv. Funct.母公司。 2023， 33， 2306328， DOI： 10.1002/adfm.202306328内容谷歌学术搜索13 催化MnWO4 纳米棒用于三阴性乳腺癌的化学动力学治疗 协同放疗赵斌;马志丽;丁帅帅;曹玉华;杜江峰;曾丽娟;胡云平;周景荣;张晓;卞秀武;田甘新功能材料 （2023 年）， 33 （47）、 2306328科登： AFMDC6; 国际标准书号：1616-301X。 （Wiley-VCH Verlag GmbH & Co. KGaA）受肿瘤微环境调节的基于纳米医学的化学动力学疗法 （CDT） 和放疗 （RT） 协同作用可实现快速肿瘤消融，这对难治性和复发性癌症（如三阴性乳腺癌 （TNBC））具有很大的希望。 克林。氧化铪 （HfO2） 的翻译，com. 命名为 NBTXR3，引起了对单组分 inorg 的新研究关注。纳米药物作为 Clin。候选人。 在此，单组分 MnWO4 首次报道为一种新型的 Fenton 样药物，但用于 TNBC 治疗的放射增敏剂，经历协同 CDT/RT 机制。 MnWO4 纳米棒是通过简单的一锅法水热法合成的，然后经过逐层聚乙二醇化以获得生物可利用的 MnWO4-PEG （MWP）。 基于 MWP 的 Fenton 样反应效率取决于反应时间、温度、pH 值和 MWP 浓度。 Mn 触发的化动力学效应延迟了 RT 诱导的 DNA 损伤修复，并将细胞周期分布分选到放射敏感期，而 W 介导的放射增敏改善了肿瘤 H2O2 过表达以增强 CDT，显着放大了细胞内氧化应激以促进 4T1 细胞凋亡。 体外和体内评估进一步证明了基于 MWP 的协同疗法的有效性和生物安全性。 考虑潜在的磁共振和计算机断层扫描。成像能力，MWP 有望在未来临床上作为成像引导癌症治疗的智能癌症诊断学。 - 14Zhang, J.; Li, X.; Han, X.; Liu, R.; Fang, J. Targeting the Thioredoxin System for Cancer Therapy. Trends Pharmacol. Sci. 2017, 38, 794– 808, DOI: 10.1016/j.tips.2017.06.001Google Scholar14https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtVWrtrbN&md5=7ef08f93d38815ed7787883c45287e9eTargeting the Thioredoxin System for Cancer TherapyZhang, Junmin; Li, Xinming; Han, Xiao; Liu, Ruijuan; Fang, JianguoTrends in Pharmacological Sciences (2017), 38 (9), 794-808CODEN: TPHSDY; ISSN:0165-6147. (Elsevier Ltd.)Thioredoxin (Trx) and thioredoxin reductase (TrxR) are essential components of the Trx system which plays pivotal roles in regulating multiple cellular redox signaling pathways. In recent years TrxR/Trx have been increasingly recognized as an important modulator of tumor development, and hence targeting TrxR/Trx is a promising strategy for cancer treatment. In this review we first discuss the structural details of TrxR, the functions of the Trx system, and the rational of targeting TrxR/Trx for cancer treatment. We also highlight small-mol. TrxR/Trx inhibitors that have potential anticancer activity and review their mechanisms of action. Finally, we examine the challenges of developing TrxR/Trx inhibitors as anticancer agents and perspectives for selectively targeting TrxR/Trx.
- 15Purohit, M. P.; Verma, N. K.; Kar, A. K.; Singh, A.; Ghosh, D.; Patnaik, S. Inhibition of Thioredoxin Reductase by Targeted Selenopolymeric Nanocarriers Synergizes the Therapeutic Efficacy of Doxorubicin in MCF7 Human Breast Cancer Cells. ACS Appl. Mater. Interfaces 2017, 9, 36493– 36512, DOI: 10.1021/acsami.7b07056Google Scholar15https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhsFGhsr%252FO&md5=1ef31302b5decc1d3e54638b05532d6dInhibition of Thioredoxin Reductase by Targeted Selenopolymeric Nanocarriers Synergizes the Therapeutic Efficacy of Doxorubicin in MCF7 Human Breast Cancer CellsPurohit, Mahaveer P.; Verma, Neeraj K.; Kar, Aditya K.; Singh, Amrita; Ghosh, Debabrata; Patnaik, SatyakamACS Applied Materials & Interfaces (2017), 9 (42), 36493-36512CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Increasing evidences suggest Selenium nanoparticles (Se NPs) as potential cancer therapeutic agents and emerging drug delivery carriers, yet, the mol. mechanism of their anticancer activity still remains unclear. Recent studies indicate, Thioredoxin Reductase (TrxR), a selenoenzyme, as a promising target for anticancer therapy. The present study explored the TrxR inhibition efficacy of Se NPs as a plausible factor impeding tumor growth. Hyaluronic acid (HA) functionalized selenopolymeric nanocarriers (Se@CMHA NPs) were designed wielding chemotherapeutic potential for target specific Doxorubicin (DOX) delivery. Se@CMHA nanocarriers are thoroughly characterized asserting their chem. and phys. integrity and possess prolonged stability. DOX loaded selenopolymeric nanocarriers (Se@CMHA-DOX NPs) exhibited enhanced cytotoxic potential towards human cancer cells compared to free DOX in an equiv. concn. eliciting selectivity towards cancer cells. In first of its kind findings, selenium as Se NPs in these polymeric carriers progressively inhibit TrxR activity, further augmenting the anticancer efficacy of DOX through a synergistic interplay between DOX and Se NPs. Detailed mol. studies on MCF7 cells also established that upon exposure to Se@CMHA-DOX NPs, MCF7 cells endure G2/M cell cycle arrest and p53 mediated caspase independent apoptosis. To gauge the relevance of the developed nanosystem in in vivo settings, 3D tumor sphere model mimicking the overall tumor environment was also carried out and the results clearly depict the effectiveness of our nanocarriers in reducing tumor activity. These findings are reminiscent of the fact that our Se@CMHA-DOX NPs could be a viable modality for effective cancer chemotherapy. interplay between DOX and Se NPs. Detailed mol. studies on MCF7 cells also established that upon exposure to Se@CMHA-DOX NPs, MCF7 cells endure G2/M cell cycle arrest and p53 mediated caspase independent apoptosis. To gauge the relevance of the developed nanosystem in actual in vivo settings, 3D tumor sphere model mimicking the overall tumor environment was also carried out and the results clearly depict the effectiveness of our nanocarriers in reducing tumor activity. These findings are reminiscent of the fact that our Se@CMHA-DOX NPs could be a viable modality for effective cancer chemotherapy.
- 16Lu, J.; Chew, E. H.; Holmgren, A. Targeting thioredoxin reductase is a basis for cancer therapy by arsenic trioxide. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 12288– 12293, DOI: 10.1073/pnas.0701549104Google Scholar16https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXos1ehsbw%253D&md5=398217220aabdc591463ad2e22a079ddTargeting thioredoxin reductase is a basis for cancer therapy by arsenic trioxideLu, Jun; Chew, Eng-hui; Holmgren, ArneProceedings of the National Academy of Sciences of the United States of America (2007), 104 (30), 12288-12293CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)Arsenic trioxide (ATO) is an effective cancer therapeutic drug for acute promyelocytic leukemia and has potential anticancer activity against a wide range of solid tumors. ATO exerts its effect mainly through elevated oxidative stress, but the exact mol. mechanism remains elusive. The thioredoxin (Trx) system comprising NADPH, thioredoxin reductase (TrxR), and Trx and the glutathione (GSH) system composed of NADPH, glutathione reductase, and GSH supported by glutaredoxin are the two electron donor systems that control cellular proliferation, viability, and apoptosis. Recently, the selenocysteine-dependent TrxR enzyme has emerged as an important mol. target for anticancer drug development. Here, we have discovered that ATO irreversibly inhibits mammalian TrxR with an IC50 of 0.25 μM. Both the N-terminal redox-active dithiol and the C-terminal selenothiol-active site of reduced TrxR may participate in the reaction with ATO. The inhibition of MCF-7 cell growth by ATO was correlated with irreversible inactivation of TrxR, which subsequently led to Trx oxidn. Furthermore, the inhibition of TrxR by ATO was attenuated by GSH, and GSH depletion by buthionine sulfoximine enhanced ATO-induced cell death. These results strongly suggest that the ATO anticancer activity is by means of a Trx system-mediated apoptosis. Blocking cancer cell DNA replication and repair and induction of oxidative stress by the inhibition of both Trx and GSH systems are suggested as cancer chemotherapeutic strategies.
- 17Sun, X.; Xu, X.; Yue, X.; Wang, T.; Wang, Z.; Zhang, C.; Wang, J. Nanozymes With Osteochondral Regenerative Effects: An Overview of Mechanisms and Recent Applications. Adv. Healthcare Mater. 2023, 13, 2301924, DOI: 10.1002/adhm.202301924Google ScholarThere is no corresponding record for this reference.
- 18Fedeli, S.; Im, J.; Gopalakrishnan, S.; Elia, J. L.; Gupta, A.; Kim, D.; Rotello, V. M. Nanomaterial-based bioorthogonal nanozymes for biological applications. Chem. Soc. Rev. 2021, 50, 13467– 13480, DOI: 10.1039/D0CS00659AGoogle Scholar18https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXisFSjtb7K&md5=7fbea0c5efcc4bfdb043be48cb49fad7Nanomaterial-based bioorthogonal nanozymes for biological applicationsFedeli, Stefano; Im, Jungkyun; Gopalakrishnan, Sanjana; Elia, James L.; Gupta, Aarohi; Kim, Dongkap; Rotello, Vincent M.Chemical Society Reviews (2021), 50 (24), 13467-13480CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)A review. Bioorthogonal transformations are chem. reactions that use pathways which biol. processes do not access. Bioorthogonal chem. provides new approaches for imaging and therapeutic strategies, as well as tools for fundamental biol. Bioorthogonal catalysis enables the development of bioorthogonal factories for on-demand and in situ generation of drugs and imaging tools. Transition metal catalysts (TMCs) are widely employed as bioorthogonal catalysts due to their high efficiency and versatility. The direct application of TMCs in living systems is challenging, however, due to their limited soly, instability in biol. media and toxicity. Incorporation of TMCs into nanomaterial scaffolds can be used to enhance aq soly, improve long-term stability in biol. environment and minimize cytotoxicity. These nanomaterial platforms can be engineered for biomedical applications, increasing cellular uptake, directing biodistribution, and enabling active targeting. This strategies for incorporating TMCs into nanomaterial scaffolds, demonstrating the potential and challenges of moving bioorthogonal nanocatalysts and nanozymes toward the clin.
- 19Huang, X.; Zhang, S.; Tang, Y.; Zhang, X.; Bai, Y.; Pang, H. Advances in metal-organic framework-based nanozymes and their applications. Coord. Chem. Rev. 2021, 449, 214216, DOI: 10.1016/j.ccr.2021.214216Google Scholar19https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXitVelsrrF&md5=a292cc5ee5b20041d01d4a24aa5f87d7Advances in metal-organic framework-based nanozymes and their applicationsHuang, Xiang; Zhang, Songtao; Tang, Yijian; Zhang, Xinyu; Bai, Yang; Pang, HuanCoordination Chemistry Reviews (2021), 449 (), 214216CODEN: CCHRAM; ISSN:0010-8545. (Elsevier B.V.)A review. Nanozymes bridge the fields of inorg. nanomaterials and biol. and have attracted wide attention. Nanozymes have the catalytic capabilities of inorg. materials at the nanoscale, and, thus, the potential to replace natural enzymes. As porous org.-inorg. coordination materials, metal-org. frameworks (MOFs) have a large no. of active sites and can mimic the properties of natural enzymes. Therefore, MOF-based nanozymes are considered to have excellent potential for biocatalysis. There are four main categories of such nanomaterials: pristine MOFs, modified MOFs, MOFs composited with natural enzymes, and MOF-derived materials. The diversity of species makes MOF-based nanozymes own wide structural variety. Not only that, diverse prepn. methods of them have been reported. These nanozymes can also be modulated by macroscopic phys. factors such as light, heat, ultrasound, and magnetic fields, which expand their applications. In this paper, the routes to prep. MOF-based nanozymes that simulate the activity of oxidases, peroxidases, catalases, superoxide dismutase, hydrolases, and multi-functional enzymes are reviewed, together with the factors influencing their catalytic activity. In addn., the applications of these nanomaterials are described, particularly those in sensing and medical treatment. Finally, we discuss possible future directions for the development of MOF-based nanozymes.
- 20Wei, H.; Gao, L.; Fan, K.; Liu, J.; He, J.; Qu, X.; Dong, S.; Wang, E.; Yan, X. Nanozymes: A clear definition with fuzzy edges. Nano Today 2021, 40, 101269, DOI: 10.1016/j.nantod.2021.101269Google Scholar20https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhvVKgurrK&md5=c9f1c526bf4e2751cd12d3ec22b57f53Nanozymes: A clear definition with fuzzy edgesWei, Hui; Gao, Lizeng; Fan, Kelong; Liu, Juewen; He, Jiuyang; Qu, Xiaogang; Dong, Shaojun; Wang, Erkang; Yan, XiyunNano Today (2021), 40 (), 101269CODEN: NTAOCG; ISSN:1748-0132. (Elsevier Ltd.)Most nanozyme research has been driven by applications, where the simple goal is the replacement of natural enzymes with more stable, cost-effective and sometimes more active nanomaterials. While in such work, nanozymes can certainly be called catalytic nanomaterials, we believe the conceptualization of these research efforts was encouraged by the name of nanozyme. nanozymes with HRP-like activity have been widely used in ELISA. The nanozyme-based ELISA had a detection limit of 0.67 pg/mL, which is approx. 110-fold better than the HRP-based ELISA. Natural enzymes often suffer from a lack of stability, preventing applications in harsh environments such as sea water or gastric acid. Nanozymes on the other hand have shown excellent stability under such conditions. Vanadium pentoxide (V2O5) nanozymes can substitute vanadium haloperoxidases for antifouling applications. Benefiting from the high stability of V2O5 nanowires, the nanozymes were painted on a stainless steel plate fixed to a boat hull and demonstrated effective suppression of biofouling in seawater for up to 60 days. Studies have also shown that nanozymes fulfill the physiol. function of natural enzymes both on the cellular and animal levels.
- 21Wang, Z.; Zhang, Y.; Ju, E.; Liu, Z.; Cao, F.; Chen, Z.; Ren, J.; Qu, X. Biomimetic nanoflowers by self-assembly of nanozymes to induce intracellular oxidative damage against hypoxic tumors. Nat. Commun. 2018, 9, 3334, DOI: 10.1038/s41467-018-05798-xGoogle Scholar21https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3c3gtVKmtw%253D%253D&md5=ccabc6752a3890498f7f40d4e2dbcc75Biomimetic nanoflowers by self-assembly of nanozymes to induce intracellular oxidative damage against hypoxic tumorsWang Zhenzhen; Zhang Yan; Ju Enguo; Liu Zhen; Cao Fangfang; Chen Zhaowei; Ren Jinsong; Qu Xiaogang; Wang Zhenzhen; Zhang Yan; Ju Enguo; Cao FangfangNature communications (2018), 9 (1), 3334 ISSN:.Reactive oxygen species (ROS)-induced apoptosis is a promising treatment strategy for malignant neoplasms. However, current systems are highly dependent on oxygen status and/or external stimuli to generate ROS, which greatly limit their therapeutic efficacy particularly in hypoxic tumors. Herein, we develop a biomimetic nanoflower based on self-assembly of nanozymes that can catalyze a cascade of intracellular biochemical reactions to produce ROS in both normoxic and hypoxic conditions without any external stimuli. In our formulation, PtCo nanoparticles are firstly synthesized and used to direct the growth of MnO2. By adjusting the ratio of reactants, highly-ordered MnO2@PtCo nanoflowers with excellent catalytic efficiency are obtained, where PtCo behaves as oxidase mimic and MnO2 functions as catalase mimic. In this way, the well-defined MnO2@PtCo nanoflowers not only can relieve hypoxic condition but also induce cell apoptosis significantly through ROS-mediated mechanism, thereby resulting in remarkable and specific inhibition of tumor growth.
- 22Yi, G.; Tao, Z.; Fan, W.; Zhou, H.; Zhuang, Q.; Wang, Y. Copper Ion-Induced Self-Assembled Aerogels of Carbon Dots as Peroxidase-Mimicking Nanozymes for Colorimetric Biosensing of Organophosphorus Pesticide. ACS Sustainable Chem. Eng. 2024, 12, 1378– 1387, DOI: 10.1021/acssuschemeng.3c04729Google ScholarThere is no corresponding record for this reference.
- 23Zhao, L.; Sun, Z.; Wang, Y.; Huang, J.; Wang, H.; Li, H.; Chang, F.; Jiang, Y. Plasmonic nanobipyramids with photo-enhanced catalytic activity under near-infrared II window for effective treatment of breast cancer. Acta Biomater. 2023, 170, 496– 506, DOI: 10.1016/j.actbio.2023.08.055Google Scholar23https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXhvVKht7zO&md5=7bb134e97fabc51db0d01839e49c4307Plasmonic nanobipyramids with photo-enhanced catalytic activity under near-infrared II window for effective treatment of breast cancerZhao, Li; Sun, Zhongqi; Wang, Yi; Huang, Jian; Wang, Haitao; Li, Hui; Chang, Fei; Jiang, YanyanActa Biomaterialia (2023), 170 (), 496-506CODEN: ABCICB; ISSN:1742-7061. (Elsevier Ltd.)Nanozyme-based catalytic therapy is an effective method for cancer treatment, but insufficient catalytic activity presents a challenge in achieving optimal therapeutic outcomes. External light can provide an innovative approach to modulate nanozyme catalytic activity. Herein, we report on plasmonic gold nanobipyramid@cuprous oxide (Au NBP@Cu2O) nanozyme for the effective phototherapy of breast cancer. In the tumor microenvironment, Cu+-mediated Fenton-like reaction catalyzes the generation of toxic hydroxyl radicals (.OH) from endogenous hydrogen peroxide to induce apoptosis. Addnl., the Au NBP@Cu2O nanostructure improves the absorption performance of Au NBPs in the near-IR II region through near-field enhancement of equipartite exciters and achieves a high photothermal conversion efficiency value of 58%. Remarkably, the Au NBP@Cu2O nanoheterostructure can capture hot electrons induced by equipartition excitations and promote electron-hole sepn. under 1064 nm laser irradn., facilitating the prodn. of more reactive oxygen species (ROS). The mechanism behind this enhanced catalytic activity was unraveled using femtosecond transient absorption spectroscopy. Both in vitro and in vivo investigations have demonstrated the efficacious tumor therapeutic potential of Au NBP@Cu2O nanozyme, particularly under 1064 nm laser irradn. Furthermore, the proposed therapeutic approach has been proved to effectively block tumor metastasis, providing a promising strategy for the development of multifunctional nanotherapeutics to tackle metastatic tumors. A highly effective plasmonic nanozyme has been developed to improve catalytic therapy for breast cancer. When exposed to 1064 nm laser irradn., Au NBP@Cu2O nanozyme can promote the sepn. of hot electrons and holes thereby facilitating the prodn. of reactive oxygen species. Hot electrons transfer behavior is unveiled by femtosecond transient absorption spectroscopy technique. This enhanced catalytic activity, along with the intrinsic photothermal effect, effectively kills tumor cells.
- 24Liu, W.; Zhang, Y.; Wei, G.; Zhang, M.; Li, T.; Liu, Q.; Zhou, Z.; Du, Y.; Wei, H. Integrated Cascade Nanozymes with Antisenescence Activities for Atherosclerosis Therapy. Angew. Chem., Int. Ed. 2023, 62, e202304465 DOI: 10.1002/anie.202304465Google Scholar24https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXhsVSqtbnP&md5=3024cec2eb30329e9367ee4f435fe5b0Integrated Cascade Nanozymes with Antisenescence Activities for Atherosclerosis TherapyLiu, Wanling; Zhang, Yihong; Wei, Gen; Zhang, Minxuan; Li, Tong; Liu, Quanyi; Zhou, Zijun; Du, Yan; Wei, HuiAngewandte Chemie, International Edition (2023), 62 (33), e202304465CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)Senescent cells are the crit. drivers of atherosclerosis formation and maturation. Mitigating senescent cells holds promise for the treatment of atherosclerosis. In an atherosclerotic plaque microenvironment, senescent cells interact with reactive oxygen species (ROS), promoting the disease development. Here, we hypothesize that a cascade nanozyme with antisenescence and antioxidant activities can serve as an effective therapeutic for atherosclerosis. An integrated cascade nanozyme with superoxide dismutase- and glutathione peroxidase-like activities, named MSe1, is developed in this work. The obtained cascade nanozyme can attenuate human umbilical vein endothelial cell (HUVEC) senescence by protecting DNA from damage. It significantly weakens inflammation in macrophages and HUVECs by eliminating overproduced intracellular ROS. Addnl., the MSe1 nanozyme effectively inhibits foam cell formation in macrophages and HUVECs by decreasing the internalization of oxidized low-d. lipoprotein. After i.v. administration, the MSe1 nanozyme significantly inhibits the formation of atherosclerosis in apolipoprotein E-deficient (ApoE-/-) mice by reducing oxidative stress and inflammation and then decreases the infiltration of inflammatory cells and senescent cells in atherosclerotic plaques. This study not only provides a cascade nanozyme but also suggests that the combination of antisenescence and antioxidative stress holds considerable promise for treating atherosclerosis.
- 25Kim, J.; Kim, H. Y.; Song, S. Y.; Go, S. H.; Sohn, H. S.; Baik, S.; Soh, M.; Kim, K.; Kim, D.; Kim, H. C.; Lee, N.; Kim, B. S.; Hyeon, T. Synergistic Oxygen Generation and Reactive Oxygen Species Scavenging by Manganese Ferrite/Ceria Co-decorated Nanoparticles for Rheumatoid Arthritis Treatment. ACS Nano 2019, 13, 3206– 3217, DOI: 10.1021/acsnano.8b08785Google Scholar25https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXktFOmsrc%253D&md5=7b5a41d29bfe2d2fc8935d15532b8c16Synergistic Oxygen Generation and Reactive Oxygen Species Scavenging by Manganese Ferrite/Ceria Co-decorated Nanoparticles for Rheumatoid Arthritis TreatmentKim, Jonghoon; Kim, Han Young; Song, Seuk Young; Go, Seok-hyeong; Sohn, Hee Su; Baik, Seungmin; Soh, Min; Kim, Kang; Kim, Dokyoon; Kim, Hyo-Cheol; Lee, Nohyun; Kim, Byung-Soo; Hyeon, TaeghwanACS Nano (2019), 13 (3), 3206-3217CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Poor O2 supply to the infiltrated immune cells in the joint synovium of rheumatoid arthritis (RA) up-regulates hypoxia-inducible factor (HIF-1α) expression and induces reactive oxygen species (ROS) generation, both of which exacerbate synovial inflammation. Synovial inflammation in RA can be resolved by eliminating pro-inflammatory M1 macrophages and inducing anti-inflammatory M2 macrophages. Because hypoxia and ROS in the RA synovium play a crucial role in the induction of M1 macrophages and redn. of M2 macrophages, herein, we develop manganese ferrite and ceria nanoparticle-anchored mesoporous silica nanoparticles (MFC-MSNs) that can synergistically scavenge ROS and produce O2 for reducing M1 macrophage levels and inducing M2 macrophages for RA treatment. MFC-MSNs exhibit a synergistic effect on O2 generation and ROS scavenging that is attributed to the complementary reaction of ceria nanoparticles (NPs) that can scavenge intermediate hydroxyl radicals generated by manganese ferrite NPs in the process of O2 generation during the Fenton reaction, leading to the efficient polarization of M1 to M2 macrophages both in vitro and in vivo. Intra-articular administration of MFC-MSNs to rat RA models alleviated hypoxia, inflammation, and pathol. features in the joint. Furthermore, MSNs were used as a drug-delivery vehicle, releasing the anti-rheumatic drug methotrexate in a sustained manner to augment the therapeutic effect of MFC-MSNs. This study highlights the therapeutic potential of MFC-MSNs that simultaneously generate O2 and scavenge ROS, subsequently driving inflammatory macrophages to the anti-inflammatory subtype for RA treatment.
- 26Liu, S.; Li, W.; Ding, H.; Tian, B.; Fang, L.; Zhao, X.; Zhao, R.; An, B.; Ding, L.; Zhong, L.; Yang, P. Biomineralized RuO2 Nanozyme with Multi-Enzyme Activity for Ultrasound-Triggered Peroxynitrite-Boosted Ferroptosis. Small 2023, 19, 2303057, DOI: 10.1002/smll.202303057Google ScholarThere is no corresponding record for this reference.
- 27Fu, R.; Ma, Z.; Zhao, H.; Jin, H.; Tang, Y.; He, T.; Ding, Y.; Zhang, J.; Ye, D. Research Progress in Iron-Based Nanozymes: Catalytic Mechanisms, Classification, and Biomedical Applications. Anal. Chem. 2023, 95, 10844– 10858, DOI: 10.1021/acs.analchem.3c01005Google ScholarThere is no corresponding record for this reference.
- 28Zou, Y.; Jin, B.; Li, H.; Wu, X.; Liu, Y.; Zhao, H.; Zhong, D.; Wang, L.; Chen, W.; Wen, M.; Liu, Y. N. Cold Nanozyme for Precise Enzymatic Antitumor Immunity. ACS Nano 2022, 16, 21491– 21504, DOI: 10.1021/acsnano.2c10057Google Scholar28https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XivF2isLfO&md5=32a48faf6fc4cdd7ab1eed431b6fd2caCold Nanozyme for Precise Enzymatic Antitumor ImmunityZou, Yuyan; Jin, Bowen; Li, Hui; Wu, Xianbo; Liu, Yihong; Zhao, Henan; Zhong, Da; Wang, Long; Chen, Wansong; Wen, Mei; Liu, You-NianACS Nano (2022), 16 (12), 21491-21504CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Precise catalysis is pursued for the biomedical applications of artificial enzymes. It is feasible to precisely control the catalysis of artificial enzymes via tunning the temp.-dependent enzymic kinetics. The safety window of cold temps. (4-37°C) for the human body is much wider than that of thermal temps. (37-42°C). Although the development of cold-activated artificial enzymes is promising, there is currently a lack of suitable candidates. Herein, a cold-activated artificial enzyme is presented with Bi2Fe4O9 nanosheets (NSs) as a paradigm. The as-obtained Bi2Fe4O9 NSs possess glutathione oxidase (GSHOx)-like activity under cold temp. due to their pyroelectricity. Bi2Fe4O9 NSs trigger the cold-enzymic death of tumor cells via apoptosis and ferroptosis, and minimize the off-target toxicity to normal tissues. Moreover, an interventional device is fabricated to intelligently and remotely control the enzymic activity of Bi2Fe4O9 NSs on a smartphone. With Bi2Fe4O9 NSs as an in situ vaccine, systemic antitumor immunity is successfully activated to suppress tumor metastasis and relapse. Moreover, blood biochem. anal. and histol. examn. indicate the high biosafety of Bi2Fe4O9 NSs for in vivo applications. This cold nanozyme provides a strategy for cancer vaccines, which can benefit the precise control over catalytic nanomedicines.
- 29James, C. C.; de Bruin, B.; Reek, J. N. H. Transition Metal Catalysis in Living Cells: Progress, Challenges, and Novel Supramolecular Solutions. Angew. Chem., Int. Ed. 2023, 62, e202306645 DOI: 10.1002/anie.202306645Google Scholar29https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXhsVCktrbL&md5=70be85b1bc7a0b959e4ac8a4e6b67729Transition Metal Catalysis in Living Cells: Progress, Challenges, and Novel Supramolecular SolutionsJames, Catriona C.; de Bruin, Bas; Reek, Joost N. H.Angewandte Chemie, International Edition (2023), 62 (41), e202306645CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. The importance of transition metal catalysis is exemplified by its wide range of applications, for example in the synthesis of chems., natural products, and pharmaceuticals. However, one relatively new application is for carrying out new-to-nature reactions inside living cells. The complex environment of a living cell is not welcoming to transition metal catalysts, as a diverse range of biol. components have the potential to inhibit or deactivate the catalyst. Here we review the current progress in the field of transition metal catalysis, and evaluation of catalysis efficiency in living cells and under biol. (relevant) conditions. Catalyst poisoning is a ubiquitous problem in this field, and we propose that future research into the development of phys. and kinetic protection strategies may provide a route to improve the reactivity of catalysts in cells.
- 30Hu, C.; Man, R.; Li, H.; Xia, M.; Yu, Z.; Tang, B. Near-Infrared Triggered Self-Accelerating Nanozyme Camouflaged with a Cancer Cell Membrane for Precise Targeted Imaging and Enhanced Cancer Immunotherapy. Anal. Chem. 2023, 95, 13575– 13585, DOI: 10.1021/acs.analchem.3c02218Google ScholarThere is no corresponding record for this reference.
- 31Gong, J.; Liu, Q.; Cai, L.; Yang, Q.; Tong, Y.; Chen, X.; Kotha, S.; Mao, X.; He, W. Multimechanism Collaborative Superior Antioxidant CDzymes To Alleviate Salt Stress-Induced Oxidative Damage in Plant Growth. ACS Sustainable Chem. Eng. 2023, 11, 4237– 4247, DOI: 10.1021/acssuschemeng.2c07371Google Scholar31https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXjslKrtLc%253D&md5=66e469f09c04f95a7e51027f7124f813Multimechanism Collaborative Superior Antioxidant CDzymes To Alleviate Salt Stress-Induced Oxidative Damage in Plant GrowthGong, Jiawen; Liu, Quan; Cai, Linlin; Yang, Qi; Tong, Yuping; Chen, Xi; Kotha, Sumasri; Mao, Xiaobo; He, WeiweiACS Sustainable Chemistry & Engineering (2023), 11 (10), 4237-4247CODEN: ASCECG; ISSN:2168-0485. (American Chemical Society)Salt stress has become one major environmental challenge threatening global crop yield. Targeting salt-induced oxidative stress, nanozymes with high-efficiency antioxidant activity and good biocompatibility represent an effective way to improve plant salt tolerance. In this study, carbon dot nanozymes (CDzymes) derived from glucose and histidine are designed to alleviate salt-induced oxidative stress in plant growth. The CDzymes are comprehensively characterized to exhibit broad-spectrum antioxidant capability, allowing them to efficiently scavenge reactive oxygen species (.OH, O2-., H2O2), reactive nitrogen species (.NO and ONOO-), and stable free radicals (DPPH., ABTS.+, PTIO.). Due to their unique structure, CDzymes exhibit multiple antioxidant mechanisms involving electron transfer, H atom transfer, and enzyme-like catalytic behavior. CDzymes have good biocompatibility and can help promote the growth of Pisum sativum Linn and Eucommia under salinity. CDzyme treatment can significantly (p < 0.001) relieve salt stress-induced oxidative damage of biol. components (including chlorophyll, proline, carbohydrate, and protein) and redox enzyme activity, which underlies the mechanism of salt-induced plant wilt. This study demonstrates that CDzymes can act as a potential antioxidant to modulate the level of oxidative stress in biol. systems, opening up new avenues for agricultural salt stress management in crops.
- 32Xu, G.; Du, X.; Wang, W.; Qu, Y.; Liu, X.; Zhao, M.; Li, W.; Li, Y. Q. Plasmonic Nanozymes: Leveraging Localized Surface Plasmon Resonance to Boost the Enzyme-Mimicking Activity of Nanomaterials. Small 2022, 18, 2204131, DOI: 10.1002/smll.202204131Google Scholar32https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XisFWrtrnP&md5=406fb3699800e814e333f34998305e2aPlasmonic Nanozymes: Leveraging Localized Surface Plasmon Resonance to Boost the Enzyme-Mimicking Activity of NanomaterialsXu, Guopeng; Du, Xuancheng; Wang, Weijie; Qu, Yuanyuan; Liu, Xiangdong; Zhao, Mingwen; Li, Weifeng; Li, Yong-QiangSmall (2022), 18 (49), 2204131CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Nanozymes, a type of nanomaterials that function similarly to natural enzymes, receive extensive attention in biomedical fields. However, the widespread applications of nanozymes are greatly plagued by their unsatisfactory enzyme-mimicking activity. Localized surface plasmon resonance (LSPR), a nanoscale phys. phenomenon described as the collective oscillation of surface free electrons in plasmonic nanoparticles under light irradn., offers a robust universal paradigm to boost the catalytic performance of nanozymes. Plasmonic nanozymes (PNzymes) with elevated enzyme-mimicking activity by leveraging LSPR, emerge and provide unprecedented opportunities for biocatalysis. In this review, the phys. mechanisms behind PNzymes are thoroughly revealed including near-field enhancement, hot carriers, and the photothermal effect. The rational design and applications of PNzymes in biosensing, cancer therapy, and bacterial infections elimination are systematically introduced. Current challenges and further perspectives of PNzymes are also summarized and discussed to stimulate their clin. translation. It is hoped that this review can attract more researchers to further advance the promising field of PNzymes and open up a new avenue for optimizing the enzyme-mimicking activity of nanozymes to create superior nanocatalysts for biomedical applications.
- 33He, T.; Jiang, C.; He, J.; Zhang, Y.; He, G.; Wu, J.; Lin, J.; Zhou, X.; Huang, P. Manganese-Dioxide-Coating-Instructed Plasmonic Modulation of Gold Nanorods for Activatable Duplex-Imaging-Guided NIR-II Photothermal-Chemodynamic Therapy. Adv. Mater. 2021, 33, 2008540, DOI: 10.1002/adma.202008540Google Scholar33https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXlsVynur4%253D&md5=b9a15a18a8f3939c590ce71f0e484ac5Manganese-Dioxide-Coating-Instructed Plasmonic Modulation of Gold Nanorods for Activatable Duplex-Imaging-Guided NIR-II Photothermal-Chemodynamic TherapyHe, Ting; Jiang, Chao; He, Jin; Zhang, Yifan; He, Gang; Wu, Jiayingzi; Lin, Jing; Zhou, Xin; Huang, PengAdvanced Materials (Weinheim, Germany) (2021), 33 (13), 2008540CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)Nanotheranostic agents of gold nanomaterials in the second near-IR (NIR-II) window have attracted significant attention in cancer management, owing to the reduced background signal and deeper penetration depth in tissues. However, it is still challenging to modulate the localized surface plasmon resonance (LSPR) of gold nanomaterials from the first near-IR (NIR-I) to NIR-II region. Herein, a plasmonic modulation strategy of gold nanorods (GNRs) through manganese dioxide coating is developed for NIR-II photoacoustic/magnetic resonance (MR) duplex-imaging-guided NIR-II photothermal chemodynamic therapy. GNRs are coated with silica dioxide (SiO2) and then covered with magnesium dioxide (MnO2) to obtain the final product of GNR@SiO2@MnO2 (denoted as GSM). The LSPR peak of GNRs could be tuned by adjusting the thickness of the MnO2 layer. Theor. simulations reveal that this plasmonic modulation is mainly due to the change of refraction index around the GNRs after coating with the MnO2 layer. Addnl., the MnO2 layer is demonstrated to degrade into Mn2+ ions in response to peroxide and acidic protons in the tumor microenvironment, which allows for MR imaging and chemodynamic therapy. This plasmonic modulation strategy can be adapted to other metal nanomaterials and the construction of a new class of NIR-II nanotheranostics.
- 34Ye, J.; Lv, W.; Li, C.; Liu, S.; Yang, X.; Zhang, J.; Wang, C.; Xu, J.; Jin, G.; Li, B.; Fu, Y.; Liang, X. Tumor Response and NIR-II Photonic Thermal Co-Enhanced Catalytic Therapy Based on Single-Atom Manganese Nanozyme. Adv. Funct. Mater. 2022, 32, 2206157, DOI: 10.1002/adfm.202206157Google Scholar34https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XisVansbjJ&md5=5efeffd7e5b8521e28e0d569e718762aTumor Response and NIR-II Photonic Thermal Co-Enhanced Catalytic Therapy Based on Single-Atom Manganese NanozymeYe, Jin; Lv, Wubin; Li, Chunsheng; Liu, Shuang; Yang, Xing; Zhang, Jiangwei; Wang, Chen; Xu, Jiating; Jin, Guanqiao; Li, Bin; Fu, Yujie; Liang, XinqiangAdvanced Functional Materials (2022), 32 (47), 2206157CODEN: AFMDC6; ISSN:1616-301X. (Wiley-VCH Verlag GmbH & Co. KGaA)Single-atom nanozymes (SAzymes) can effectively mimic the metal active centers of natural enzymes at the at. level owing to their atomically dispersed active sites, thereby maximizing atom utilization efficiency and d. of active sites. Hence, SAzymes can be considered the most promising candidates to replace natural enzymes. Herein, a PEGylated mesoporous Mn-based single-atom nanozyme (PmMn/SAE) employing a coordination-assisted polymn. pyrolysis strategy that uses polydopamine for photothermal-augmented nanocatalytic therapy is designed. PmMn/SAE exhibits excellent multiple enzymic performance, including catalase-like, oxidase-like, and peroxidase (POD)-like performance, due to the atomically dispersed Mn active species. As a result, PmMn/SAE not only catalyzes the decompn. of endogenous H2O2 to generate O2 for relieving hypoxia inside the tumor but also transfers electrons to O2 to produce superoxide radicals to kill tumor cells. Meanwhile, PmMn/SAE is able to trigger Fenton-like reactions to generate highly toxic hydroxyl radicals to induce cancer cell apoptosis. The POD-like catalytic mechanism of mMn/SAE is revealed using exptl. results and d. functional theory. Furthermor, PmMn/SAE shows good photothermal conversion efficiency (η = 22.1%) in the second near-IR region (1064 nm). Both the in vitro and in vivo exptl. results indicate that PmMn/SAE can effectively kill cancer cells through photothermal-enhanced catalytic therapy.
- 35An, L.; Wang, C.; Tian, Q.; Tao, C.; Xue, F.; Yang, S.; Zhou, X.; Chen, X.; Huang, G. NIR-II laser-mediated photo-Fenton-like reaction via plasmonic Cu9S8 for immunotherapy enhancement. Nano Today 2022, 43, 101397, DOI: 10.1016/j.nantod.2022.101397Google Scholar35https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XhtFKksbvO&md5=9e857951fb701bbf746754e7291017bcNIR-II laser-mediated photo-Fenton-like reaction via plasmonic Cu9S8 for immunotherapy enhancementAn, Lu; Wang, Chengbin; Tian, Qiwei; Tao, Cheng; Xue, Fengfeng; Yang, Shiping; Zhou, Xuesu; Chen, Xiaoyuan; Huang, GangNano Today (2022), 43 (), 101397CODEN: NTAOCG; ISSN:1748-0132. (Elsevier Ltd.)Chemodynamic therapy (CDT) is typically used to modulate the immunogenic tumor microenvironment and extend the benefits of immune checkpoint therapy because of its good tumor selectivity. However, the poor catalytic efficiency of CDT agents means that it often needs to be combined with other enhancement strategies, such as radiotherapy and photothermal therapy with high power d., which can inevitably traumatize normal tissues. To overcome these limitations, a near-IR (NIR)-II laser-mediated photo-Fenton-like reaction based on a plasmonic self-doped semiconductor was proposed as a mild enhancement strategy to enhance the immune responses. Exptl. simulations and results of plasmonic Cu9S8 show that the NIR-II laser can enhance the CDT effect based on the plasmon-driven photoredox chem. without inducing a photothermal effect. Furthermore, the enhanced CDT effectively induces immunogenic cell death and dendritic cell maturation both in vitro and in vivo. In addn., the antitumor immune response is greatly enhanced by the synergistic effect of the NIR-II laser in enhancing both CDT and anti-PD-L1. This allows for primary tumor elimination and the effective suppression of distant tumors and lung metastases. Our proposed design indicates that the NIR-II photo-Fenton-like reaction based on the plasmonic semiconductor effectively enhances CDT, thus selectively enhancing immunotherapy.
- 36Li, S.; Shang, L.; Xu, B.; Wang, S.; Gu, K.; Wu, Q.; Sun, Y.; Zhang, Q.; Yang, H.; Zhang, F.; Gu, L.; Zhang, T.; Liu, H. A Nanozyme with Photo-Enhanced Dual Enzyme-Like Activities for Deep Pancreatic Cancer Therapy. Angew. Chem., Int. Ed. 2019, 58, 12624– 12631, DOI: 10.1002/anie.201904751Google Scholar36https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhsFSrt7bJ&md5=c682101dc0351d49ad5ab1c3951d6877A nanozyme with photo-enhanced dual enzyme-like activities for deep pancreatic cancer therapyLi, Shanshan; Shang, Lu; Xu, Bolong; Wang, Shunhao; Gu, Kai; Wu, Qingyuan; Sun, Yun; Zhang, Qinghua; Yang, Hailong; Zhang, Fengrong; Gu, Lin; Zhang, Tierui; Liu, HuiyuAngewandte Chemie, International Edition (2019), 58 (36), 12624-12631CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)Nanozymes have attracted extensive interest owing to their high stability, low cost and easy prepn., esp. in the field of cancer therapy. However, the relatively low catalytic activity of nanozymes in the tumor microenvironment (TME) has limited their applications. Herein, we report a novel nanozyme (PtFe@Fe3O4) with dual enzyme-like activities for highly efficient tumor catalytic therapy. PtFe@Fe3O4 shows the intrinsic photothermal effect as well as photo-enhanced peroxidase-like and catalase-like activities in the acidic TME, thereby effectively killing tumor cells and overcoming the tumor hypoxia. Importantly, a possible photo-enhanced synergistic catalytic mechanism of PtFe@Fe3O4 was first disclosed. We believe that this work will advance the development of nanozymes in tumor catalytic therapy.
- 37Meng, X.; Sun, S.; Gong, C.; Yang, J.; Yang, Z.; Zhang, X.; Dong, H. Ag-Doped Metal-Organic Frameworks’ Heterostructure for Sonodynamic Therapy of Deep-Seated Cancer and Bacterial Infection. ACS Nano 2023, 17, 1174– 1186, DOI: 10.1021/acsnano.2c08687Google ScholarThere is no corresponding record for this reference.
- 38Oh, W. D.; Lok, L. W.; Veksha, A.; Giannis, A.; Lim, T. T. Enhanced photocatalytic degradation of bisphenol A with Ag-decorated S-doped g-C3N4 under solar irradiation: Performance and mechanistic studies. Chem. Eng. J. 2018, 333, 739– 749, DOI: 10.1016/j.cej.2017.09.182Google Scholar38https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhslOis7bJ&md5=25d3315cccece80c10442b8c9ffe8c66Enhanced photocatalytic degradation of bisphenol A with Ag-decorated S-doped g-C3N4 under solar irradiation: Performance and mechanistic studiesOh, Wen-Da; Lok, Li-Wen; Veksha, Andrei; Giannis, Apostolos; Lim, Teik-ThyeChemical Engineering Journal (Amsterdam, Netherlands) (2018), 333 (), 739-749CODEN: CMEJAJ; ISSN:1385-8947. (Elsevier B.V.)Ag-decorated S-doped g-C3N4 composites with different % wt./wt. Ag were synthesized via chem. redn. method. The Ag/S-doped g-C3N4 composites were used as photocatalysts for aq. bisphenol A (BPA) degrdn. under solar irradn. Investigation of the photocatalysts using various characterization methods including X-ray diffractometry, SEM and transmission electron microscopy indicated that the Ag nanoparticles (av. size = 10-20 nm) were well-cryst. and uniformly distributed on the S-doped g-C3N4 (SCN) surface. The photocatalytic performance of SCN was ∼3 times more efficient than that of the g-C3N4, while the Ag/SCN with 12% wt./wt. Ag (Ag-SCN-12) exhibited the highest photocatalytic activity for BPA degrdn. followed by 8% wt./wt. Ag/SCN, 4% wt./wt. Ag/SCN, SCN, and Ag. The effects of pH and Ag-SCN-12 loading on photocatalytic BPA degrdn. were also investigated. The results showed that the Ag-SCN-12 was highly stable (<40 μg L-1 Ag leaching) and could be reused for at least 4 cycles without significant deterioration to its catalytic activity. The incorporation of Ag into the SCN enhanced the photocatalytic activity of SCN due to the improved electron-hole pair sepn. and decreased electron-hole pair recombination rate as evidenced by the photoluminescence emission study. The predominant reactive oxygen species (ROS) generated by the Ag-SCN-12 photocatalytic system was O·-2 which formed secondary ROS (·OH, and 1O2) for BPA degrdn. The mechanism of ROS generation during the photocatalytic process is also proposed. Based on the BPA degrdn. intermediates identified using the LC/MS/MS, the BPA degrdn. pathways in the photocatalytic system are elucidated.
- 39Wang, N.; Li, P.; Zhao, J.; Liu, Y.; Hu, X.; Ling, D.; Li, F. An anisotropic photocatalytic agent elicits robust photoimmunotherapy through plasmonic catalysis-mediated tumor microenvironment modulation. Nano Today 2023, 50, 101827, DOI: 10.1016/j.nantod.2023.101827Google ScholarThere is no corresponding record for this reference.
- 40Hasan, A. A.; Kalinina, E.; Tatarskiy, V.; Shtil, A. The Thioredoxin System of Mammalian Cells and Its Modulators. Biomedicines 2022, 10, 1757, DOI: 10.3390/biomedicines10071757Google ScholarThere is no corresponding record for this reference.
- 41Zeisel, L.; Felber, J. G.; Scholzen, K. C.; Poczka, L.; Cheff, D.; Maier, M. S.; Cheng, Q.; Shen, M.; Hall, M. D.; Arnér, E. S. J.; Thorn-Seshold, J.; Thorn-Seshold, O. Selective cellular probes for mammalian thioredoxin reductase TrxR1: Rational design of RX1, a modular 1,2-thiaselenane redox probe. Chem. 2022, 8, 1493– 1517, DOI: 10.1016/j.chempr.2022.03.010Google ScholarThere is no corresponding record for this reference.
- 42Srivastava, M.; Singh, S.; Self, W. T. Exposure to Silver Nanoparticles Inhibits Selenoprotein Synthesis and the Activity of Thioredoxin Reductase. Environ. Health Perspect. 2012, 120, 56– 61, DOI: 10.1289/ehp.1103928Google ScholarThere is no corresponding record for this reference.
- 43Pang, M.; Zeng, H. C. Highly Ordered Self-Assemblies of Submicrometer Cu2O Spheres and Their Hollow Chalcogenide Derivatives. Langmuir 2010, 26, 5963– 5970, DOI: 10.1021/la904292tGoogle Scholar43https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXisFGnu7g%253D&md5=e436544f3d9b416eeea4d1152bf3c33eHighly Ordered Self-Assemblies of Submicrometer Cu2O Spheres and Their Hollow Chalcogenide DerivativesPang, Maolin; Zeng, Hua ChunLangmuir (2010), 26 (8), 5963-5970CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)Highly ordered superlattices assembled from transition metal oxide/sulfide submicrometer particles are difficult to prep. due to lack of monodisperse primary building blocks. In this work, we have successfully synthesized monodisperse Cu2O spheres with diams. in the submicrometer regime of 130-135 nm. Using the as-prepd. Cu2O spheres as solid precursor, uniform hollow CuS and CuSe derivs. have also been synthesized in soln. media. More importantly, a range of two-dimensional and three-dimensional superlattices of Cu2O, CuS, and CuSe solid/hollow spheres have been assembled for the first time. Without assistance of conventional sacrificing solid templates, the degree of ordering achieved in these superlattices is comparable to those reported for well-studied silica and polystyrene beads. The realization of these self-assembled superlattices may provide a new way of thin film design and fabrication for this class of photosensitive semiconducting materials using their prefabricated building blocks.
- 44Mao, Z.; Yang, Z.; Tao, W.; Tang, Q.; Xiao, Y.; Jiang, Y.; Guo, S. Ultrafine Ag Nanoparticles Anchored on Hollow S-Doped CeO2 Spheres for Synergistically Enhanced Tetracycline Degradation under Visible Light. Ind. Eng. Chem. Res. 2022, 61, 17092– 17101, DOI: 10.1021/acs.iecr.2c02674Google ScholarThere is no corresponding record for this reference.
- 45Guo, Y.; Wang, H.; Ma, X.; Jin, J.; Ji, W.; Wang, X.; Song, W.; Zhao, B.; He, C. Fabrication of Ag-Cu2O/Reduced Graphene Oxide Nanocomposites as Surface-Enhanced Raman Scattering Substrates for in Situ Monitoring of Peroxidase-Like Catalytic Reaction and Biosensing. ACS Appl. Mater. Interfaces 2017, 9, 19074– 19081, DOI: 10.1021/acsami.7b02149Google Scholar45https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXns1OnsrY%253D&md5=37b758771fd78dec577f66fa42c48febFabrication of Ag-Cu2O/Reduced Graphene Oxide Nanocomposites as Surface-Enhanced Raman Scattering Substrates for in Situ Monitoring of Peroxidase-Like Catalytic Reaction and BiosensingGuo, Yue; Wang, Hai; Ma, Xiaowei; Jin, Jing; Ji, Wei; Wang, Xu; Song, Wei; Zhao, Bing; He, ChengyanACS Applied Materials & Interfaces (2017), 9 (22), 19074-19081CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Highly sensitive biosensors are essential in medical diagnostics, esp. for monitoring the state of an individual's disease. An ideal way to achieve this objective is to analyze human sweat secretions by non-invasive monitoring. Due to low concns. of target analytes in human secretions, fabrication of ultra-sensitive detection devices is a great challenge. In this work, Ag-Cu2O/reduced graphene oxide (rGO) nanocomposites are prepd. by a facile two-step in situ redn. procedure at room temp. Ag-Cu2O/rGO nanocomposites possess intrinsic peroxidase-like activity and rapidly catalyze oxidn. of the peroxidase substrate 3, 3', 5, 5'-tetramethylbenzidine (TMB) in the presence of H2O2. On the basis of the excellent SERS properties and high peroxidase-like activity of the Ag-Cu2O/rGO nanocomposites, the catalytic oxidn. of TMB can be monitored by SERS. This approach can detect H2O2 and glucose with high sensitivity and distinguish between diabetic and normal individuals using glucose levels in fingerprints. Our work provides direction for designing other SERS substrates with high catalytic activity and the potential for application in biosensing, forensic investigation, and medical diagnostics.
- 46Rasheed, M.; Saira, F.; Batool, Z.; khan, H. M.; Yaseen, J.; Arshad, M.; Kalsoom, A.; Ahmeda, H. E.; Naeem Ashiq, M. N. Facile synthesis of a CuSe/PVP nanocomposite for ultrasensitive non-enzymatic glucose biosensing. RSC Adv. 2023, 13, 26755– 26765, DOI: 10.1039/d3ra03175fGoogle ScholarThere is no corresponding record for this reference.
- 47Kayed, K.; Mayada Issa, M.; Al-ourabi, H. The FTIR spectra of Ag/Ag2O composites doped with silver nanoparticles. J. Exp. Nanosci. 2024, 19, 2336227, DOI: 10.1080/17458080.2024.2336227Google ScholarThere is no corresponding record for this reference.
- 48Abu-Elsaad, N. I.; Nawara, A. S.; Mazen, S. A. Synthesis, structural characterization, and magnetic properties of Ni-Zn nanoferrites substituted with different metal ions (Mn2+, Co2+, and Cu2+). J. Phys. Chem. Solids 2020, 146, 109620, DOI: 10.1016/j.jpcs.2020.109620Google ScholarThere is no corresponding record for this reference.
- 49Khurana, A.; Tekula, S.; Saifi, M. A.; Venkatesh, P.; Godugu, C. Therapeutic applications of selenium nanoparticles. Pharmacother. 2019, 111, 802– 812, DOI: 10.1016/j.biopha.2018.12.146Google Scholar 谷歌学术There is no corresponding record for this reference.
49库拉纳，A.;Tekula， S.;马萨诸塞州 Saifi;文卡特什，P.;戈杜古 C. 硒纳米颗粒的治疗应用。药剂师。 2019， 111， 802– 812， DOI： 10.1016/j.biopha.2018.12.146谷歌学术此参考没有相应的记录。 - 50Zhang, X. L.; Hu, S. J.; Zheng, Y. R.; Wu, R.; Gao, F. Y.; Yang, P. P.; Niu, Z. Z.; Gu, C.; Yu, X.; Zheng, X. S.; Ma, C.; Zheng, X.; Zhu, J. F.; Gao, M. R.; Yu, S. H. Polymorphic cobalt diselenide as extremely stable electrocatalyst in acidic media via a phase-mixing strategy. Nat. Commun. 2019, 10, 5338, DOI: 10.1038/s41467-019-12992-yGoogle Scholar 谷歌学术50https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3Mfjt1aisw%253D%253D&md5=5bc60ba5d2d1645d89b95f8ddb9066f6Polymorphic cobalt diselenide as extremely stable electrocatalyst in acidic media via a phase-mixing strategyZhang Xiao-Long; Zheng Ya-Rong; Wu Rui; Gao Fei-Yue; Yang Peng-Peng; Niu Zhuang-Zhuang; Gu Chao; Yu Xingxing; Gao Min-Rui; Yu Shu-Hong; Hu Shao-Jin; Zheng Xiao; Zheng Xu-Sheng; Zhu Jun-Fa; Ma Cheng; Yu Shu-HongNature communications (2019), 10 (1), 5338 ISSN:.Many platinum group metal-free inorganic catalysts have demonstrated high intrinsic activity for diverse important electrode reactions, but their practical use often suffers from undesirable structural degradation and hence poor stability, especially in acidic media. We report here an alkali-heating synthesis to achieve phase-mixed cobalt diselenide material with nearly homogeneous distribution of cubic and orthorhombic phases. Using water electroreduction as a model reaction, we observe that the phase-mixed cobalt diselenide reaches the current density of 10 milliamperes per square centimeter at overpotential of mere 124 millivolts in acidic electrolyte. The catalyst shows no sign of deactivation after more than 400 h of continuous operation and the polarization curve is well retained after 50,000 potential cycles. Experimental and computational investigations uncover a boosted covalency between Co and Se atoms resulting from the phase mixture, which substantially enhances the lattice robustness and thereby the material stability. The findings provide promising design strategy for long-lived catalysts in acid through crystal phase engineering.
50张 X. L.;胡， SJ;郑，YR;吴，R.;高，FY;杨，PP;牛，ZZ;顾 C.;于，X.;郑，XS;马，C.;郑 X.;朱，JF;高，MR;余 S. H. 多晶型二硒化钴作为酸性介质中极其稳定的电催化剂，通过相混合策略。Nat. Commun. 2019， 10， 5338， DOI： 10.1038/s41467-019-12992-y内容谷歌学术搜索50https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3Mfjt1aisw%253D%253D&md5=5bc60ba5d2d1645d89b95f8ddb9066f6 的更多多晶型二硒化钴作为酸性介质中极其稳定的电催化剂，通过相混合策略Zhang Xiao-Long;郑亚荣;吴瑞;高飞跃;杨鹏鹏;牛壮壮;顾超;于兴兴;高敏瑞;余淑红;胡绍金;郑晓;郑旭生;朱俊发;马程;Yu Shu-HongNature 通讯 （2019 年）， 10 （1）、 5338 元 国际标准书号：.许多铂族无金属无机催化剂已显示出对各种重要电极反应的高本征活性，但它们的实际使用往往会受到不良结构降解的影响，因此稳定性差，尤其是在酸性介质中。 我们在这里报道了一种碱热合成，以获得具有几乎均匀分布的立方相和斜方相的相混合二硒化钴材料。 使用水电还原作为模型反应，我们观察到相混合二硒化钴在酸性电解质中，在仅 124 毫伏的过电位下达到每平方厘米 10 毫安的电流密度。 催化剂在连续运行超过 400 小时后没有失活迹象，并且在 50,000 次电位循环后极化曲线保持良好。 实验和计算研究发现，相混合物导致 Co 和 Se 原子之间的共价性增强，这大大增强了晶格的稳健性，从而提高了材料的稳定性。 研究结果为通过晶相工程在酸中长寿命催化剂提供了有前途的设计策略。 - 51Yang, C.; Wang, M.; Chang, M.; Yuan, M.; Zhang, W.; Tan, J.; Ding, B.; Ma, P. a.; Lin, J. Heterostructural Nanoadjuvant CuSe/CoSe2 for Potentiating Ferroptosis and Photoimmunotherapy through Intratumoral Blocked Lactate Efflux. J. Am. Chem. Soc. 2023, 145, 7205– 7217, DOI: 10.1021/jacs.2c12772Google Scholar51https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXlvVOhsLs%253D&md5=730aaa576b690335b0b061a70b01afa9Heterostructural Nanoadjuvant CuSe/CoSe2 for Potentiating Ferroptosis and Photoimmunotherapy through Intratumoral Blocked Lactate EffluxYang, Chunzheng; Wang, Man; Chang, Mengyu; Yuan, Meng; Zhang, Wenying; Tan, Jia; Ding, Binbin; Ma, Ping'an; Lin, JunJournal of the American Chemical Society (2023), 145 (13), 7205-7217CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)The desirable curative effect in clin. immunotherapy has been challenging due to the immunosuppressive tumor microenvironment (TME) with high lactic acid (LA) metab. in solid tumors. Although targeting metabolic reprogramming of tumor cells can restore the survival and function of immune cells in the TME, it is also plagued by insufficient immunogenicity. Herein, an activatable immunomodulatory nanoadjuvant CuSe/CoSe2@syrosingopine (CSC@Syro) is constructed for simultaneously relieving immunosuppressive TME and boosting tumor immune response. Specifically, CuSe/CoSe2 (CSC) exhibits TME-activated glutathione (GSH) depletion and hydroxyl radical (•OH) generation for potential ferroptosis. Meanwhile, the remarkable photothermal conversion efficiency and elevated photocatalytic ROS level both promote CSC heterostructures to induce robust immunogenic cell death (ICD). Besides, the loaded syrosingopine inhibitor achieves LA metab. blockade in cancer cells by downregulating the expression of monocarboxylate transporter 4 (MCT4), which could sensitize ferroptosis by intracellular milieu acidification and neutralize the acidic TME to alleviate immunosuppression. Hence, advanced metabolic modulation confers the potentiated immune infiltration of ICD-stimulated T lymphocytes and further reinforces antitumor therapy. In brief, CSC@Syro-mediated synergistic therapy could elicit potent immunogenicity and suppress tumor proliferation and metastasis effectually by integrating the tumor metabolic regulation and ferroptosis with immunotherapy.
51杨 C.;王 M.;张，M.;袁 M.;张 W.;谭 J.;丁 B.;宾夕法尼亚州马;林 J. 异质结构纳米辅助 CuSe/CoSe2 通过瘤内阻断乳酸外排增强铁死亡和光免疫治疗。J. Am. Chem. Soc. 2023， 145， 7205– 7217， DOI： 10.1021/jacs.2c12772Google Scholar51？origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXlvVOhsLs%253D&md5=730aaa576b690335b0b061a70b01afa9异质结构纳米辅助 CuSe/CoSe2 通过瘤内阻断乳酸外排增强铁死亡和光免疫治疗Yang， Chunzheng;王曼;张梦玉;袁孟;张文英;谭佳;丁彬彬;马， 平安;Lin， Jun美国化学会杂志 （2023 年）， 票价：145 （13）、 7205-7217科登： JACSAT公司; 国际标准书号：0002-7863。 （美国化学学会）由于实体瘤中具有高乳酸 （LA） 代谢的免疫抑制性肿瘤微环境 （TME），临床免疫疗法的理想疗效一直具有挑战性。 虽然靶向肿瘤细胞的代谢重编程可以恢复 TME 中免疫细胞的存活和功能，但也受到免疫原性不足的困扰。 在此，构建了一种可激活的免疫调节纳米佐剂 CuSe/CoSe2@syrosingopine （CSC@Syro），用于同时缓解免疫抑制性 TME 和增强肿瘤免疫反应。 具体来说，CuSe/CoSe2 （CSC） 表现出 TME 激活的谷胱甘肽 （GSH） 耗竭和羟基自由基 （•OH） 的产生，用于潜在的铁死亡。 同时，显着的光热转换效率和升高的光催化 ROS 水平都促进了 CSC 异质结构诱导稳健的免疫原性细胞死亡 （ICD）。 此外，负载的 syrosingopine 抑制剂达到 LA metab。通过下调单羧酸转运蛋白 4 （MCT4） 的表达来阻断癌细胞，MCT4 可以通过细胞内环境酸化使铁死亡敏感，并中和酸性 TME 以减轻免疫抑制。 因此，先进的代谢调节增强了 ICD 刺激的 T 淋巴细胞的免疫浸润，并进一步加强了抗肿瘤治疗。 简而言之，CSC@Syro介导的协同治疗可以通过将肿瘤代谢调节和铁死亡与免疫治疗相结合，引发有效的免疫原性并有效抑制肿瘤增殖和转移。 - 52Ji, R.; Sun, W.; Chu, Y. One-step hydrothermal synthesis of Ag/Cu2O heterogeneous nanostructures over Cu foil and their SERS applications. RSC Adv. 2014, 4, 6055– 6059, DOI: 10.1039/c3ra44281kGoogle Scholar52https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXls1WgsA%253D%253D&md5=c866d55f6b19a4a48bb0b83390eea95eOne-step hydrothermal synthesis of Ag/Cu2O heterogeneous nanostructures over Cu foil and their SERS applicationsJi, Ran; Sun, Wendong; Chu, YingRSC Advances (2014), 4 (12), 6055-6059CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)In this paper, Ag/Cu2O heterogeneous nanostructured films (HNFs) were prepd. by a one-step hydrothermal method. It involved only two materials, AgNO3 and Cu foil, in the aq. soln. to form Ag/Cu2O HNF. X-ray diffraction (XRD), XPS, energy dispersive x-ray spectroscopy (EDX), SEM (SEM), transmission electron microscopy (TEM) and high-resoln. transmission electron microscopy (HRTEM) were used to characterize the Ag/Cu2O films. Ag nanoparticles and Cu2O nanocubes were formed by redox reactions and the Ag nanoparticles deposited on the Cu2O nanocubes via electrostatic attraction. The obtained Ag/Cu2O HNF was found to be a good candidate for SERS application.
- 53Liu, J.; Zhang, X.; Wen, B.; Li, Y.; Wu, J.; Wang, Z.; Wu, T.; Zhao, R.; Yang, S. Pre-carbonized nitrogen-rich polytriazines for the controlled growth of silver nanoparticles: catalysts for enhanced CO2 chemical conversion at atmospheric pressure. Catal. Sci. Technol. 2021, 11, 3119– 3127, DOI: 10.1039/D0CY02473BGoogle Scholar53https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXlt1aks7c%253D&md5=a37325413de88843ab6fc12d2fb04b4cPre-carbonized nitrogen-rich polytriazines for the controlled growth of silver nanoparticles: catalysts for enhanced CO2 chemical conversion at atmospheric pressureLiu, Jian; Zhang, Xiaoyi; Wen, Bingyan; Li, Yipei; Wu, Jingjing; Wang, Zhipeng; Wu, Ting; Zhao, Rusong; Yang, ShenghongCatalysis Science & Technology (2021), 11 (9), 3119-3127CODEN: CSTAGD; ISSN:2044-4753. (Royal Society of Chemistry)High catalytic activity and sufficient durability are two unavoidable key indexes of an efficient heterogeneous catalyst for the direct carboxylation of terminal alkynes with CO2 conversion. Nitrogen-rich covalent triazine frameworks (CTFs) are promising substrates, while random distribution of some residual -NH2 groups brings challenges to the controlled growth of catalytic species. Here, we adopt a pre-carbonization protocol, annealing below the carbonization temp., to eliminate the random -NH2 groups in CTFs and meanwhile to promote polycondensation degree under the premise of maintaining the pore structure. Benefiting from the improved condensation and orderly N atoms, p-CTF-250, for which CTFs are annealed at 250°C, exhibits improved CO2 adsorption capacity and the ability to control the growth of Ag NPs. Mono-dispersed Ag NPs are generated controllably and entrapped to form Ag@p-CTF-250 catalysts. These Ag@p-CTF-250 catalysts were employed in the direct carboxylation of various terminal alkynes with CO2 under mild conditions (50°C, 1 atm) and showed excellent catalytic activity. In addn., these catalysts have robust recyclability and can be used for at least 5 catalytic runs while retaining yield above 90%. CO2 conversion proceeds well under the synergistic effect between the high CO2 capture capability and the uniform tiny Ag NPs in Ag@p-CTF-250 "nanoreactors". The results represent an efficient strategy for controlling the growth of metallic nanoparticles in porous org. polymer substrates contg. disordered heteroatoms.
- 54Yu, B.; Zhou, Y.; Li, P.; Tu, W.; Li, P.; Tang, L.; Ye, J.; Zou, Z. Photocatalytic reduction of CO2 over Ag/TiO2 nanocomposites prepared with a simple and rapid silver mirror method. Nanoscale 2016, 8, 11870– 11874, DOI: 10.1039/C6NR02547AGoogle Scholar54https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XnvFOitbc%253D&md5=6b6f70710d765bcc3e55734dc2364c48Photocatalytic reduction of CO2 over Ag/TiO2 nanocomposites prepared with a simple and rapid silver mirror methodYu, Bingcheng; Zhou, Yong; Li, Peng; Tu, Wenguang; Li, Ping; Tang, Lanqin; Ye, Jinhua; Zou, ZhigangNanoscale (2016), 8 (23), 11870-11874CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)The photocatalytic redn. of CO2 over Ag/TiO2 composites prepd. with a simple silver mirror reaction method was investigated under UV-visible irradn. in both gas-phase (CO2 + water vapor) and aq. soln. (CO2-satd. NaHCO3 soln.) systems. The as-prepd. Ag/TiO2 nanocomposite exhibits efficient photocatalytic activity due to the surface plasmonic resonance and electron sink effect of the Ag component, which was found to be closely related to the size and loading amt. of Ag. The rapid silver method is effective at curbing the size of Ag, so photocatalytic activity can be improved. Diverse org. chem. products were detected, including mainly methane and methanol as well as a small amt. of C2 and C3 species such as acetaldehyde and acetone. Possible photocatalytic mechanisms were proposed. This artificial photosynthesis process may give a prosperous route to the removal of CO2 while simultaneously converting CO2 to valuable fuels based on highly efficient photocatalysts.
- 55Sathishkumar, K.; Sowmiya, K.; Arul Pragasan, L.; Rajagopal, R.; Sathya, R.; Ragupathy, S.; Krishnakumar, M.; Minnam Reddy, V. R. Enhanced photocatalytic degradation of organic pollutants by Ag-TiO2 loaded cassava stem activated carbon under sunlight irradiation. Chemosphere 2022, 302, 134844, DOI: 10.1016/j.chemosphere.2022.134844Google ScholarThere is no corresponding record for this reference.
- 56Wang, C.; Cao, F. J.; Ruan, Y.; Jia, X.; Zhen, W.; Jiang, X. Specific Generation of Singlet Oxygen through the Russell Mechanism in Hypoxic Tumors and GSH Depletion by Cu-TCPP Nanosheets for Cancer Therapy. Angew. Chem. 2019, 131, 9951– 9955, DOI: 10.1002/ange.201903981Google ScholarThere is no corresponding record for this reference.
- 57Chiang, C.; Chu, K.; Lin, C.; Xie, S.; Liu, Y.; Demeshko, S.; Lee, G.; Meyer, F.; Tsai, M.; Chiang, M.; Chien-Ming Lee, C. Photoinduced NO and HNO Production from Mononuclear {FeNO}6 Complex Bearing a Pendant Thiol. J. Am. Chem. Soc. 2020, 142, 8649– 8661, DOI: 10.1021/jacs.9b13837Google Scholar57https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXmvFGhu74%253D&md5=02e22fb6eb688a5eee00349ea9816167Photoinduced NO and HNO production from mononuclear {FeNO}6 complex bearing a pendant thiolChiang, Chuan-Kuei; Chu, Kai-Ti; Lin, Chia-Chin; Xie, Shi-Rou; Liu, Yu-Chiao; Demeshko, Serhiy; Lee, Gene-Hsiang; Meyer, Franc; Tsai, Ming-Li; Chiang, Ming-Hsi; Lee, Chien-MingJournal of the American Chemical Society (2020), 142 (19), 8649-8661CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Light triggers the formation of HNO from a metal-nitrosyl species, facilitated by an intramol. pendant thiol proton. Two {FeNO}6 complexes (the Enemark-Felthan notation), [Fe(NO)(TMSPS2)(TMSPS2H)] (1, TMSPS2H2 = 2,2'-dimercapto-3,3'-bis((trimethylsilyl)diphenyl)phenylphosphine; H is a dissociable proton) with a pendant thiol and [Fe(NO)(TMSPS2)(TMSPS2CH3)] (2) bearing a pendant thioether, are spectroscopically and structurally characterized. Both complexes are highly sensitive to visible light. Upon photolysis, complex 2 undergoes NO dissocn. to yield a mononuclear Fe(III) complex, [Fe(TMSPS2)(TMSPS2CH3)] (3). In contrast, the pendant SH of 1 can act as a trap for the departing NO radical upon irradn., resulting in the formation of an intermediate A with an intramol. [SH···ON-Fe] interaction. As suggested by computational results (d. functional theory), the NO stretching frequency (νNO) is sensitive to the intramol. interaction between the pendant ligand and the iron-bound NO, and a shift of νNO from 1833 (1) to 1823 cm-1 (A) is obsd. exptl. Subsequent photolysis of the intermediate A results in HNO prodn. and a thiyl group that then coordinates to the Fe center for the formation of [Fe(TMSPS2)2] (4). In contrast with the common acid-base coupling pathway, the HNO is not voluntarily yielded from 1 but rather is generated by the photopromoted pathway. The photogenerated HNO can further react with [MnIII(TMSPS3)(DABCO)] TMSPS3H3 = (2,2'2''-trimercapto-3,3',3''-tris(trimethylsilyl)triphenylphosphine; DABCO = 1,4-diazabicyclo[2.2.2]octane) in org. media to yield anionic [Mn(NO)(TMSPS3)]- (5-) with a {MnNO}6 electronic configuration, whereas [MnIII(TMSPS3)(DABCO)] reacts with NO gas for the formation of a {MnNO}5 species, [Mn(NO)(TMSPS3)] (6). Effective differentiation of the formation of HNO from complex 1 with the pendant SH vs. NO from 2 with the pendant SMe is achieved by the employment of [MnIII(TMSPS3)(DABCO)].
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Abstract
Scheme 1
Scheme 1. Illustration of (A) Synthetic Process of CSA and (B) Proposed Antitumor Mechanism of CSA for Improved Photothermal TherapyFigure 1
Figure 1. TEM images of (A) Cu2O NPs, (B) CS NPs, and (C) CSA NPs. (D) HR-TEM image of CSA. (E) HAADF-STEM image and elemental mappings of Cu, Se, and Ag elements in CSA NPs. (F) XRD spectra for Cu2O NPs, CS NPs, and CSA NPs. (G) Full XPS spectra for CS and CSA. High-resolution XPS spectra for (H) Cu 2p, (I) Se 3d, and (J) Ag 3d in CSA.
Figure 2
Figure 2. (A) Relative activity of TrxR enzyme with the treatment of different amounts of CSA (n = 3). (B) Time-dependent UV/vis absorption changes of DTNB treated with CSA (50 μg/mL) in a PBS solution containing GSH (10 mM). (C) Photothermal heating curves of CSA with different concentrations under 1064 nm laser (1.0 W/cm2). (D) Temperature curves of CSA (50 μg/mL) with a 1064 nm laser of different power irradiation for different times. (E) Recycling–heating profiles of CSA solution (50 μg/mL) under cyclic on/off laser irradiation. (F) Temperature elevation and cooling curves of CSA solution (50 μg/mL) after 5 min of irradiation (1.0 W/cm2) and linear regression data obtained from the cooling period. ESR spectra of (G) DMPO/•OH, (H) DMPO/•O2–, and (I) TEMP/1O2, treated with H2O2, CSA, or NIR irradiation under different conditions.
Figure 3
Figure 3. (A) Cell viability of A549 cells treated with different concentrations of CSA under different conditions. Error bars represent standard deviation for n = 5; P values were based on Student’s t-test: ****P < 0.0001, ***P < 0.001, **P < 0.01, and *P < 0.05. (B) Fluorescence images of calcein AM (green, live cells, Ex = 488 nm) and PI (red, dead cells, Ex = 552 nm) costained A549 cells after incubation with various concentrations of CSA for 24 h. Scale bars: 250 μm. (C) Confocal microscopy images of A549 cells with HPF, DHE, and SOSG to study the •OH, •O2–, and 1O2 generation, respectively, in the presence of CSA (15 μg/mL) with or without laser (Ex = 488 nm). Scale bars: 50 μm.
Figure 4
Figure 4. CLSM images of (A) GPX4, (B) TRFS-green, (C) C11-BODIPY581/591, (D) TF2-DEVD-FMK, and (E) AO-stained A549 cells treated with CSA at different concentrations. Scale bars: 50 μm.
Figure 5
Figure 5. In vivo therapeutic effect and metastasis inhibition of CSA. (A) Infrared thermal images at the tumor sites of mice. Changes in the relative body weight (B), tumor volume (C), and tumor weight (D) of mice with different treatments (n = 6). (E) Photographs of tumors dissected from each group of mice on the 14th day. (F) Micrographs of H & E stained and TUNEL stained tumor slices on the 14th day in different groups (scale bar: 250 μm). Error bars represent standard deviation for n = 5; P values were based on Student’s t-test: ****P < 0.0001, ***P < 0.001, **P < 0.01, and *P < 0.05.
References
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- 8Wang, Z.; Wei, M.; Liu, Q.; Lu, X.; Zhou, J.; Wang, J. Oxygen-defective zinc oxide nanoparticles as highly efficient and safe sonosensitizers for cancer therapy. Chem. Commun. 2023, 59, 10968– 10971, DOI: 10.1039/D3CC02486EThere is no corresponding record for this reference.
- 9Wang, Y.; Tang, Q.; Wu, R.; Sun, S.; Zhang, J.; Chen, J.; Gong, M.; Chen, C.; Liang, X. Ultrasound-Triggered Piezocatalysis for Selectively Controlled NO Gas and Chemodrug Release to Enhance Drug Penetration in Pancreatic Cancer. ACS Nano 2023, 17, 3557– 3573, DOI: 10.1021/acsnano.2c099489https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXivFWltL8%253D&md5=685ba2078bacec5a050551bc42116c5bUltrasound-Triggered Piezocatalysis for Selectively Controlled NO Gas and Chemodrug Release to Enhance Drug Penetration in Pancreatic CancerWang, Yuan; Tang, Qingshuang; Wu, Ruiqi; Sun, Suhui; Zhang, Jinxia; Chen, Jing; Gong, Ming; Chen, Chaoyi; Liang, XiaolongACS Nano (2023), 17 (4), 3557-3573CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Nitric oxide (NO) is drawing widespread attention in treating pancreatic ductal adenocarcinoma (PDAC) as a safe and therapeutically efficient technique through modulating the dense fibrotic stroma in the tumor microenvironment to enhance drug penetration. Considerable NO nanogenerators and NO releasing mols. have been developed to shield the systemic toxicity caused by free diffusion of NO gas. However, on-demand controlled release of NO and chemotherapy drugs at tumor sites remains a problem limited by the complex and dynamic tumor microenvironment. Herein, we present an ultrasound-responsive nanoprodrug of CPT-t-R-PEG2000@BaTiO3 (CRB) which encapsulates piezoelec. nanomaterials barium titanate nanoparticle (BaTiO3) with amphiphilic prodrug mols. that consisted of thioketal bond (t) linked chemotherapy drug camptothecin (CPT) and NO-donor L-arginine (R). Based on ultrasound-triggered piezocatalysis, BaTiO3 can continuously generate ROS in the hypoxic tumor environment, which induces a cascade of reaction processes to break the thioketal bond to release CPT and oxidize R to release NO, simultaneously delivering CPT and NO to the tumor site. It is revealed that CRB shows a uniform size distribution, prolonged blood circulation time, and excellent tumor targeting ability. Moreover, controlled release of CPT and NO were obsd. both in vitro and in vivo under the stimulation of ultrasound, which is beneficial to the depletion of dense stroma and subsequently enhanced delivery and efficacy of CPT. Taken together, CRB significantly increased the antitumor efficacy against highly malignant Panc02 tumors in mice through inhibiting chemoresistance, representing a feasible approach for targeted therapies against Panc02 and other PDAC.
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- 11Zhang, R.; Ma, Q.; Hu, G.; Wang, L. Acid-Triggered H2O2 Self-Supplying Nanoplatform for 19F-MRI with Enhanced Chemo-Chemodynamic Therapy. Anal. Chem. 2022, 94, 3727– 3734, DOI: 10.1021/acs.analchem.2c0002311https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XktVKhu7s%253D&md5=52076fd08320b4bf0ae541506b392cdbAcid-Triggered H2O2 Self-Supplying Nanoplatform for 19F-MRI with Enhanced Chemo-Chemodynamic TherapyZhang, Ruijuan; Ma, Qian; Hu, Gaofei; Wang, LeyuAnalytical Chemistry (Washington, DC, United States) (2022), 94 (8), 3727-3734CODEN: ANCHAM; ISSN:0003-2700. (American Chemical Society)The real-time tracking and efficacy evaluation of therapeutic nanoplatforms esp. in deep-tissues is of great importance but faces challenges. Meanwhile, chemodynamic therapy (CDT), relying on Fenton reaction by converting H2O2 into toxic hydroxyl radicals (.OH), has drawn wide interests in the fabrication of nanozymes for tumor therapy, while endogenous H2O2 is usually insufficient for effective CDT. Here, we report the pH-responsive multifunctional nanoplatforms consisting of copper peroxide (CP) nanoparticles, paclitaxel (PTX) and perfluoro-15-crown-5-ether (PFCE), for 19F magnetic resonance imaging guided and enhanced chemo-chemodynamic synergetic therapy with self-supplied H2O2 stemmed from the decompn. of CP nanoparticles under acid conditions in tumor. The decompn. of CP nanoparticles further promotes the release of PTX for enhanced chemotherapy. Both in vitro and in vivo results indicate that the efficient generation of .OH and drug release effectively inhibits tumor growth. Furthermore, 19F MRI signal can clearly track the fate of nanoplatforms in tumor and guide tumor treatment. This work provides a promising strategy for the rational design and construction of multifunctional nanoplatforms for imaging-guided synergistic therapy of deep seated tumor.
- 12Zhang, Y.; Zhang, Q.; Wang, F.; Li, M.; Shi, X.; Li, J. Activatable Semiconducting Polymer Nanoinducers Amplify Oxidative Damage via Sono-Ferroptosis for Synergistic Therapy of Bone Metastasis. Nano Lett. 2023, 23, 7699– 7708, DOI: 10.1021/acs.nanolett.3c0241412https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXhs1Gqu7%252FE&md5=638377aa513934f506dc4b2ae3a2c2bcActivatable Semiconducting Polymer Nanoinducers Amplify Oxidative Damage via Sono-Ferroptosis for Synergistic Therapy of Bone MetastasisZhang, Yijing; Zhang, Qin; Wang, Fengshuo; Li, Meng; Shi, Xiangyang; Li, JingchaoNano Letters (2023), 23 (16), 7699-7708CODEN: NALEFD; ISSN:1530-6984. (American Chemical Society)Bone metastases are secondary malignant tumors that commonly occur after the spread of advanced cancer cells. We herein report the activatable semiconducting polymer nanoinducers (ASPNFP) that can amplify oxidative damage via sono-ferroptosis for bone metastasis treatment. ASPNFP are constructed by encapsulating plasma amine oxidase-based semiconducting polymer nanoparticles (SPNP) and Fe3O4 nanoparticles into singlet oxygen (1O2)-responsive nanocarriers. ASPNFP generate 1O2 under ultrasound (US) irradn. via a sonodynamic effect to destroy the stability of 1O2-responsive nanocarriers, allowing US-triggered releases of SPNP and Fe3O4 nanoparticles. SPNP decomp. polyamines in tumor cells to produce acrolein and hydrogen peroxide (H2O2), in which H2O2 promotes Fenton reaction mediated by Fe3O4 nanoparticles for inducing enhanced ferroptosis and generation of hydroxyl radicals (.OH). The generated acrolein, 1O2, and .OH can simultaneously amplify the oxidative damage. ASPNFP thus mediate an amplified sono-ferroptosis effect to inhibit the growth of bone metastasis and restrict tumor metastasis.
- 13Zhao, B.; Ma, Z.; Ding, S.; Cao, Y.; Du, J.; Zeng, L.; Hu, Y.; Zhou, J.; Zhang, X.; Bian, X. w.; Tian, G. Catalytic MnWO4 Nanorods for Chemodynamic Therapy Synergized Radiotherapy of Triple Negative Breast Cancer. Adv. Funct. Mater. 2023, 33, 2306328, DOI: 10.1002/adfm.20230632813https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXhsVKltbfL&md5=881fa424ae7244d6187de7d6afbb5d5dCatalytic MnWO4 Nanorods for Chemodynamic Therapy Synergized Radiotherapy of Triple Negative Breast CancerZhao, Bin; Ma, Zhili; Ding, Shuaishuai; Cao, Yuhua; Du, Jiangfeng; Zeng, Lijuan; Hu, Yunping; Zhou, Jingrong; Zhang, Xiao; Bian, Xiu-wu; Tian, GanAdvanced Functional Materials (2023), 33 (47), 2306328CODEN: AFMDC6; ISSN:1616-301X. (Wiley-VCH Verlag GmbH & Co. KGaA)Nanomedicine-based synergy of chemodynamic therapy (CDT) and radiotherapy (RT) modulated by tumor microenvironment enables rapid tumor ablation, which holds great hope for the refractory and recurrent cancers, such as triple neg. breast cancer (TNBC). The clin. translation of hafnium oxide (HfO2), com. named as NBTXR3, has aroused new research focus on single-component inorg. nanomedicines as clin. candidates. Herein, the single-component MnWO4 is first reported as a new kind of Fenton-like agent yet radiosensitizer for TNBC treatment undergoing the synergistic CDT/RT mechanism. MnWO4 nanorods are synthesized via a simple one-pot hydrothermal method and then undergo a layer-by-layer PEGylation to obtain bioavailable MnWO4-PEG (MWP). MWP-based Fenton-like reaction efficacy depends on reaction time, temps., pH values, and MWP concns. Mn-triggered chemodynamic effect delays RT-induced DNA damage repair and sorts cell cycles distribution toward radiosensitive phases, while W-mediated radiosensitization improves the tumoral H2O2 overexpression to enhance CDT, remarkably amplifying of the intracellular oxidative stress to boost 4T1 cell apoptosis. In vitro and in vivo evaluations further demonstrate the effectiveness and biosafety of MWP-based synergistic therapy. Considering the potential magnetic resonance and computed tomog. imaging capabilities, MWP can be expected as an intelligent cancer theranostics for imaging-guided cancer therapy in clinic in the future.
- 14Zhang, J.; Li, X.; Han, X.; Liu, R.; Fang, J. Targeting the Thioredoxin System for Cancer Therapy. Trends Pharmacol. Sci. 2017, 38, 794– 808, DOI: 10.1016/j.tips.2017.06.00114https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhtVWrtrbN&md5=7ef08f93d38815ed7787883c45287e9eTargeting the Thioredoxin System for Cancer TherapyZhang, Junmin; Li, Xinming; Han, Xiao; Liu, Ruijuan; Fang, JianguoTrends in Pharmacological Sciences (2017), 38 (9), 794-808CODEN: TPHSDY; ISSN:0165-6147. (Elsevier Ltd.)Thioredoxin (Trx) and thioredoxin reductase (TrxR) are essential components of the Trx system which plays pivotal roles in regulating multiple cellular redox signaling pathways. In recent years TrxR/Trx have been increasingly recognized as an important modulator of tumor development, and hence targeting TrxR/Trx is a promising strategy for cancer treatment. In this review we first discuss the structural details of TrxR, the functions of the Trx system, and the rational of targeting TrxR/Trx for cancer treatment. We also highlight small-mol. TrxR/Trx inhibitors that have potential anticancer activity and review their mechanisms of action. Finally, we examine the challenges of developing TrxR/Trx inhibitors as anticancer agents and perspectives for selectively targeting TrxR/Trx.
- 15Purohit, M. P.; Verma, N. K.; Kar, A. K.; Singh, A.; Ghosh, D.; Patnaik, S. Inhibition of Thioredoxin Reductase by Targeted Selenopolymeric Nanocarriers Synergizes the Therapeutic Efficacy of Doxorubicin in MCF7 Human Breast Cancer Cells. ACS Appl. Mater. Interfaces 2017, 9, 36493– 36512, DOI: 10.1021/acsami.7b0705615https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhsFGhsr%252FO&md5=1ef31302b5decc1d3e54638b05532d6dInhibition of Thioredoxin Reductase by Targeted Selenopolymeric Nanocarriers Synergizes the Therapeutic Efficacy of Doxorubicin in MCF7 Human Breast Cancer CellsPurohit, Mahaveer P.; Verma, Neeraj K.; Kar, Aditya K.; Singh, Amrita; Ghosh, Debabrata; Patnaik, SatyakamACS Applied Materials & Interfaces (2017), 9 (42), 36493-36512CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Increasing evidences suggest Selenium nanoparticles (Se NPs) as potential cancer therapeutic agents and emerging drug delivery carriers, yet, the mol. mechanism of their anticancer activity still remains unclear. Recent studies indicate, Thioredoxin Reductase (TrxR), a selenoenzyme, as a promising target for anticancer therapy. The present study explored the TrxR inhibition efficacy of Se NPs as a plausible factor impeding tumor growth. Hyaluronic acid (HA) functionalized selenopolymeric nanocarriers (Se@CMHA NPs) were designed wielding chemotherapeutic potential for target specific Doxorubicin (DOX) delivery. Se@CMHA nanocarriers are thoroughly characterized asserting their chem. and phys. integrity and possess prolonged stability. DOX loaded selenopolymeric nanocarriers (Se@CMHA-DOX NPs) exhibited enhanced cytotoxic potential towards human cancer cells compared to free DOX in an equiv. concn. eliciting selectivity towards cancer cells. In first of its kind findings, selenium as Se NPs in these polymeric carriers progressively inhibit TrxR activity, further augmenting the anticancer efficacy of DOX through a synergistic interplay between DOX and Se NPs. Detailed mol. studies on MCF7 cells also established that upon exposure to Se@CMHA-DOX NPs, MCF7 cells endure G2/M cell cycle arrest and p53 mediated caspase independent apoptosis. To gauge the relevance of the developed nanosystem in in vivo settings, 3D tumor sphere model mimicking the overall tumor environment was also carried out and the results clearly depict the effectiveness of our nanocarriers in reducing tumor activity. These findings are reminiscent of the fact that our Se@CMHA-DOX NPs could be a viable modality for effective cancer chemotherapy. interplay between DOX and Se NPs. Detailed mol. studies on MCF7 cells also established that upon exposure to Se@CMHA-DOX NPs, MCF7 cells endure G2/M cell cycle arrest and p53 mediated caspase independent apoptosis. To gauge the relevance of the developed nanosystem in actual in vivo settings, 3D tumor sphere model mimicking the overall tumor environment was also carried out and the results clearly depict the effectiveness of our nanocarriers in reducing tumor activity. These findings are reminiscent of the fact that our Se@CMHA-DOX NPs could be a viable modality for effective cancer chemotherapy.
- 16Lu, J.; Chew, E. H.; Holmgren, A. Targeting thioredoxin reductase is a basis for cancer therapy by arsenic trioxide. Proc. Natl. Acad. Sci. U.S.A. 2007, 104, 12288– 12293, DOI: 10.1073/pnas.070154910416https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXos1ehsbw%253D&md5=398217220aabdc591463ad2e22a079ddTargeting thioredoxin reductase is a basis for cancer therapy by arsenic trioxideLu, Jun; Chew, Eng-hui; Holmgren, ArneProceedings of the National Academy of Sciences of the United States of America (2007), 104 (30), 12288-12293CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)Arsenic trioxide (ATO) is an effective cancer therapeutic drug for acute promyelocytic leukemia and has potential anticancer activity against a wide range of solid tumors. ATO exerts its effect mainly through elevated oxidative stress, but the exact mol. mechanism remains elusive. The thioredoxin (Trx) system comprising NADPH, thioredoxin reductase (TrxR), and Trx and the glutathione (GSH) system composed of NADPH, glutathione reductase, and GSH supported by glutaredoxin are the two electron donor systems that control cellular proliferation, viability, and apoptosis. Recently, the selenocysteine-dependent TrxR enzyme has emerged as an important mol. target for anticancer drug development. Here, we have discovered that ATO irreversibly inhibits mammalian TrxR with an IC50 of 0.25 μM. Both the N-terminal redox-active dithiol and the C-terminal selenothiol-active site of reduced TrxR may participate in the reaction with ATO. The inhibition of MCF-7 cell growth by ATO was correlated with irreversible inactivation of TrxR, which subsequently led to Trx oxidn. Furthermore, the inhibition of TrxR by ATO was attenuated by GSH, and GSH depletion by buthionine sulfoximine enhanced ATO-induced cell death. These results strongly suggest that the ATO anticancer activity is by means of a Trx system-mediated apoptosis. Blocking cancer cell DNA replication and repair and induction of oxidative stress by the inhibition of both Trx and GSH systems are suggested as cancer chemotherapeutic strategies.
- 17Sun, X.; Xu, X.; Yue, X.; Wang, T.; Wang, Z.; Zhang, C.; Wang, J. Nanozymes With Osteochondral Regenerative Effects: An Overview of Mechanisms and Recent Applications. Adv. Healthcare Mater. 2023, 13, 2301924, DOI: 10.1002/adhm.202301924There is no corresponding record for this reference.
- 18Fedeli, S.; Im, J.; Gopalakrishnan, S.; Elia, J. L.; Gupta, A.; Kim, D.; Rotello, V. M. Nanomaterial-based bioorthogonal nanozymes for biological applications. Chem. Soc. Rev. 2021, 50, 13467– 13480, DOI: 10.1039/D0CS00659A18https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXisFSjtb7K&md5=7fbea0c5efcc4bfdb043be48cb49fad7Nanomaterial-based bioorthogonal nanozymes for biological applicationsFedeli, Stefano; Im, Jungkyun; Gopalakrishnan, Sanjana; Elia, James L.; Gupta, Aarohi; Kim, Dongkap; Rotello, Vincent M.Chemical Society Reviews (2021), 50 (24), 13467-13480CODEN: CSRVBR; ISSN:0306-0012. (Royal Society of Chemistry)A review. Bioorthogonal transformations are chem. reactions that use pathways which biol. processes do not access. Bioorthogonal chem. provides new approaches for imaging and therapeutic strategies, as well as tools for fundamental biol. Bioorthogonal catalysis enables the development of bioorthogonal factories for on-demand and in situ generation of drugs and imaging tools. Transition metal catalysts (TMCs) are widely employed as bioorthogonal catalysts due to their high efficiency and versatility. The direct application of TMCs in living systems is challenging, however, due to their limited soly, instability in biol. media and toxicity. Incorporation of TMCs into nanomaterial scaffolds can be used to enhance aq soly, improve long-term stability in biol. environment and minimize cytotoxicity. These nanomaterial platforms can be engineered for biomedical applications, increasing cellular uptake, directing biodistribution, and enabling active targeting. This strategies for incorporating TMCs into nanomaterial scaffolds, demonstrating the potential and challenges of moving bioorthogonal nanocatalysts and nanozymes toward the clin.
- 19Huang, X.; Zhang, S.; Tang, Y.; Zhang, X.; Bai, Y.; Pang, H. Advances in metal-organic framework-based nanozymes and their applications. Coord. Chem. Rev. 2021, 449, 214216, DOI: 10.1016/j.ccr.2021.21421619https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXitVelsrrF&md5=a292cc5ee5b20041d01d4a24aa5f87d7Advances in metal-organic framework-based nanozymes and their applicationsHuang, Xiang; Zhang, Songtao; Tang, Yijian; Zhang, Xinyu; Bai, Yang; Pang, HuanCoordination Chemistry Reviews (2021), 449 (), 214216CODEN: CCHRAM; ISSN:0010-8545. (Elsevier B.V.)A review. Nanozymes bridge the fields of inorg. nanomaterials and biol. and have attracted wide attention. Nanozymes have the catalytic capabilities of inorg. materials at the nanoscale, and, thus, the potential to replace natural enzymes. As porous org.-inorg. coordination materials, metal-org. frameworks (MOFs) have a large no. of active sites and can mimic the properties of natural enzymes. Therefore, MOF-based nanozymes are considered to have excellent potential for biocatalysis. There are four main categories of such nanomaterials: pristine MOFs, modified MOFs, MOFs composited with natural enzymes, and MOF-derived materials. The diversity of species makes MOF-based nanozymes own wide structural variety. Not only that, diverse prepn. methods of them have been reported. These nanozymes can also be modulated by macroscopic phys. factors such as light, heat, ultrasound, and magnetic fields, which expand their applications. In this paper, the routes to prep. MOF-based nanozymes that simulate the activity of oxidases, peroxidases, catalases, superoxide dismutase, hydrolases, and multi-functional enzymes are reviewed, together with the factors influencing their catalytic activity. In addn., the applications of these nanomaterials are described, particularly those in sensing and medical treatment. Finally, we discuss possible future directions for the development of MOF-based nanozymes.
- 20Wei, H.; Gao, L.; Fan, K.; Liu, J.; He, J.; Qu, X.; Dong, S.; Wang, E.; Yan, X. Nanozymes: A clear definition with fuzzy edges. Nano Today 2021, 40, 101269, DOI: 10.1016/j.nantod.2021.10126920https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXhvVKgurrK&md5=c9f1c526bf4e2751cd12d3ec22b57f53Nanozymes: A clear definition with fuzzy edgesWei, Hui; Gao, Lizeng; Fan, Kelong; Liu, Juewen; He, Jiuyang; Qu, Xiaogang; Dong, Shaojun; Wang, Erkang; Yan, XiyunNano Today (2021), 40 (), 101269CODEN: NTAOCG; ISSN:1748-0132. (Elsevier Ltd.)Most nanozyme research has been driven by applications, where the simple goal is the replacement of natural enzymes with more stable, cost-effective and sometimes more active nanomaterials. While in such work, nanozymes can certainly be called catalytic nanomaterials, we believe the conceptualization of these research efforts was encouraged by the name of nanozyme. nanozymes with HRP-like activity have been widely used in ELISA. The nanozyme-based ELISA had a detection limit of 0.67 pg/mL, which is approx. 110-fold better than the HRP-based ELISA. Natural enzymes often suffer from a lack of stability, preventing applications in harsh environments such as sea water or gastric acid. Nanozymes on the other hand have shown excellent stability under such conditions. Vanadium pentoxide (V2O5) nanozymes can substitute vanadium haloperoxidases for antifouling applications. Benefiting from the high stability of V2O5 nanowires, the nanozymes were painted on a stainless steel plate fixed to a boat hull and demonstrated effective suppression of biofouling in seawater for up to 60 days. Studies have also shown that nanozymes fulfill the physiol. function of natural enzymes both on the cellular and animal levels.
- 21Wang, Z.; Zhang, Y.; Ju, E.; Liu, Z.; Cao, F.; Chen, Z.; Ren, J.; Qu, X. Biomimetic nanoflowers by self-assembly of nanozymes to induce intracellular oxidative damage against hypoxic tumors. Nat. Commun. 2018, 9, 3334, DOI: 10.1038/s41467-018-05798-x21https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3c3gtVKmtw%253D%253D&md5=ccabc6752a3890498f7f40d4e2dbcc75Biomimetic nanoflowers by self-assembly of nanozymes to induce intracellular oxidative damage against hypoxic tumorsWang Zhenzhen; Zhang Yan; Ju Enguo; Liu Zhen; Cao Fangfang; Chen Zhaowei; Ren Jinsong; Qu Xiaogang; Wang Zhenzhen; Zhang Yan; Ju Enguo; Cao FangfangNature communications (2018), 9 (1), 3334 ISSN:.Reactive oxygen species (ROS)-induced apoptosis is a promising treatment strategy for malignant neoplasms. However, current systems are highly dependent on oxygen status and/or external stimuli to generate ROS, which greatly limit their therapeutic efficacy particularly in hypoxic tumors. Herein, we develop a biomimetic nanoflower based on self-assembly of nanozymes that can catalyze a cascade of intracellular biochemical reactions to produce ROS in both normoxic and hypoxic conditions without any external stimuli. In our formulation, PtCo nanoparticles are firstly synthesized and used to direct the growth of MnO2. By adjusting the ratio of reactants, highly-ordered MnO2@PtCo nanoflowers with excellent catalytic efficiency are obtained, where PtCo behaves as oxidase mimic and MnO2 functions as catalase mimic. In this way, the well-defined MnO2@PtCo nanoflowers not only can relieve hypoxic condition but also induce cell apoptosis significantly through ROS-mediated mechanism, thereby resulting in remarkable and specific inhibition of tumor growth.
- 22Yi, G.; Tao, Z.; Fan, W.; Zhou, H.; Zhuang, Q.; Wang, Y. Copper Ion-Induced Self-Assembled Aerogels of Carbon Dots as Peroxidase-Mimicking Nanozymes for Colorimetric Biosensing of Organophosphorus Pesticide. ACS Sustainable Chem. Eng. 2024, 12, 1378– 1387, DOI: 10.1021/acssuschemeng.3c04729There is no corresponding record for this reference.
- 23Zhao, L.; Sun, Z.; Wang, Y.; Huang, J.; Wang, H.; Li, H.; Chang, F.; Jiang, Y. Plasmonic nanobipyramids with photo-enhanced catalytic activity under near-infrared II window for effective treatment of breast cancer. Acta Biomater. 2023, 170, 496– 506, DOI: 10.1016/j.actbio.2023.08.05523https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXhvVKht7zO&md5=7bb134e97fabc51db0d01839e49c4307Plasmonic nanobipyramids with photo-enhanced catalytic activity under near-infrared II window for effective treatment of breast cancerZhao, Li; Sun, Zhongqi; Wang, Yi; Huang, Jian; Wang, Haitao; Li, Hui; Chang, Fei; Jiang, YanyanActa Biomaterialia (2023), 170 (), 496-506CODEN: ABCICB; ISSN:1742-7061. (Elsevier Ltd.)Nanozyme-based catalytic therapy is an effective method for cancer treatment, but insufficient catalytic activity presents a challenge in achieving optimal therapeutic outcomes. External light can provide an innovative approach to modulate nanozyme catalytic activity. Herein, we report on plasmonic gold nanobipyramid@cuprous oxide (Au NBP@Cu2O) nanozyme for the effective phototherapy of breast cancer. In the tumor microenvironment, Cu+-mediated Fenton-like reaction catalyzes the generation of toxic hydroxyl radicals (.OH) from endogenous hydrogen peroxide to induce apoptosis. Addnl., the Au NBP@Cu2O nanostructure improves the absorption performance of Au NBPs in the near-IR II region through near-field enhancement of equipartite exciters and achieves a high photothermal conversion efficiency value of 58%. Remarkably, the Au NBP@Cu2O nanoheterostructure can capture hot electrons induced by equipartition excitations and promote electron-hole sepn. under 1064 nm laser irradn., facilitating the prodn. of more reactive oxygen species (ROS). The mechanism behind this enhanced catalytic activity was unraveled using femtosecond transient absorption spectroscopy. Both in vitro and in vivo investigations have demonstrated the efficacious tumor therapeutic potential of Au NBP@Cu2O nanozyme, particularly under 1064 nm laser irradn. Furthermore, the proposed therapeutic approach has been proved to effectively block tumor metastasis, providing a promising strategy for the development of multifunctional nanotherapeutics to tackle metastatic tumors. A highly effective plasmonic nanozyme has been developed to improve catalytic therapy for breast cancer. When exposed to 1064 nm laser irradn., Au NBP@Cu2O nanozyme can promote the sepn. of hot electrons and holes thereby facilitating the prodn. of reactive oxygen species. Hot electrons transfer behavior is unveiled by femtosecond transient absorption spectroscopy technique. This enhanced catalytic activity, along with the intrinsic photothermal effect, effectively kills tumor cells.
- 24Liu, W.; Zhang, Y.; Wei, G.; Zhang, M.; Li, T.; Liu, Q.; Zhou, Z.; Du, Y.; Wei, H. Integrated Cascade Nanozymes with Antisenescence Activities for Atherosclerosis Therapy. Angew. Chem., Int. Ed. 2023, 62, e202304465 DOI: 10.1002/anie.20230446524https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXhsVSqtbnP&md5=3024cec2eb30329e9367ee4f435fe5b0Integrated Cascade Nanozymes with Antisenescence Activities for Atherosclerosis TherapyLiu, Wanling; Zhang, Yihong; Wei, Gen; Zhang, Minxuan; Li, Tong; Liu, Quanyi; Zhou, Zijun; Du, Yan; Wei, HuiAngewandte Chemie, International Edition (2023), 62 (33), e202304465CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)Senescent cells are the crit. drivers of atherosclerosis formation and maturation. Mitigating senescent cells holds promise for the treatment of atherosclerosis. In an atherosclerotic plaque microenvironment, senescent cells interact with reactive oxygen species (ROS), promoting the disease development. Here, we hypothesize that a cascade nanozyme with antisenescence and antioxidant activities can serve as an effective therapeutic for atherosclerosis. An integrated cascade nanozyme with superoxide dismutase- and glutathione peroxidase-like activities, named MSe1, is developed in this work. The obtained cascade nanozyme can attenuate human umbilical vein endothelial cell (HUVEC) senescence by protecting DNA from damage. It significantly weakens inflammation in macrophages and HUVECs by eliminating overproduced intracellular ROS. Addnl., the MSe1 nanozyme effectively inhibits foam cell formation in macrophages and HUVECs by decreasing the internalization of oxidized low-d. lipoprotein. After i.v. administration, the MSe1 nanozyme significantly inhibits the formation of atherosclerosis in apolipoprotein E-deficient (ApoE-/-) mice by reducing oxidative stress and inflammation and then decreases the infiltration of inflammatory cells and senescent cells in atherosclerotic plaques. This study not only provides a cascade nanozyme but also suggests that the combination of antisenescence and antioxidative stress holds considerable promise for treating atherosclerosis.
- 25Kim, J.; Kim, H. Y.; Song, S. Y.; Go, S. H.; Sohn, H. S.; Baik, S.; Soh, M.; Kim, K.; Kim, D.; Kim, H. C.; Lee, N.; Kim, B. S.; Hyeon, T. Synergistic Oxygen Generation and Reactive Oxygen Species Scavenging by Manganese Ferrite/Ceria Co-decorated Nanoparticles for Rheumatoid Arthritis Treatment. ACS Nano 2019, 13, 3206– 3217, DOI: 10.1021/acsnano.8b0878525https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXktFOmsrc%253D&md5=7b5a41d29bfe2d2fc8935d15532b8c16Synergistic Oxygen Generation and Reactive Oxygen Species Scavenging by Manganese Ferrite/Ceria Co-decorated Nanoparticles for Rheumatoid Arthritis TreatmentKim, Jonghoon; Kim, Han Young; Song, Seuk Young; Go, Seok-hyeong; Sohn, Hee Su; Baik, Seungmin; Soh, Min; Kim, Kang; Kim, Dokyoon; Kim, Hyo-Cheol; Lee, Nohyun; Kim, Byung-Soo; Hyeon, TaeghwanACS Nano (2019), 13 (3), 3206-3217CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Poor O2 supply to the infiltrated immune cells in the joint synovium of rheumatoid arthritis (RA) up-regulates hypoxia-inducible factor (HIF-1α) expression and induces reactive oxygen species (ROS) generation, both of which exacerbate synovial inflammation. Synovial inflammation in RA can be resolved by eliminating pro-inflammatory M1 macrophages and inducing anti-inflammatory M2 macrophages. Because hypoxia and ROS in the RA synovium play a crucial role in the induction of M1 macrophages and redn. of M2 macrophages, herein, we develop manganese ferrite and ceria nanoparticle-anchored mesoporous silica nanoparticles (MFC-MSNs) that can synergistically scavenge ROS and produce O2 for reducing M1 macrophage levels and inducing M2 macrophages for RA treatment. MFC-MSNs exhibit a synergistic effect on O2 generation and ROS scavenging that is attributed to the complementary reaction of ceria nanoparticles (NPs) that can scavenge intermediate hydroxyl radicals generated by manganese ferrite NPs in the process of O2 generation during the Fenton reaction, leading to the efficient polarization of M1 to M2 macrophages both in vitro and in vivo. Intra-articular administration of MFC-MSNs to rat RA models alleviated hypoxia, inflammation, and pathol. features in the joint. Furthermore, MSNs were used as a drug-delivery vehicle, releasing the anti-rheumatic drug methotrexate in a sustained manner to augment the therapeutic effect of MFC-MSNs. This study highlights the therapeutic potential of MFC-MSNs that simultaneously generate O2 and scavenge ROS, subsequently driving inflammatory macrophages to the anti-inflammatory subtype for RA treatment.
- 26Liu, S.; Li, W.; Ding, H.; Tian, B.; Fang, L.; Zhao, X.; Zhao, R.; An, B.; Ding, L.; Zhong, L.; Yang, P. Biomineralized RuO2 Nanozyme with Multi-Enzyme Activity for Ultrasound-Triggered Peroxynitrite-Boosted Ferroptosis. Small 2023, 19, 2303057, DOI: 10.1002/smll.202303057There is no corresponding record for this reference.
- 27Fu, R.; Ma, Z.; Zhao, H.; Jin, H.; Tang, Y.; He, T.; Ding, Y.; Zhang, J.; Ye, D. Research Progress in Iron-Based Nanozymes: Catalytic Mechanisms, Classification, and Biomedical Applications. Anal. Chem. 2023, 95, 10844– 10858, DOI: 10.1021/acs.analchem.3c01005There is no corresponding record for this reference.
- 28Zou, Y.; Jin, B.; Li, H.; Wu, X.; Liu, Y.; Zhao, H.; Zhong, D.; Wang, L.; Chen, W.; Wen, M.; Liu, Y. N. Cold Nanozyme for Precise Enzymatic Antitumor Immunity. ACS Nano 2022, 16, 21491– 21504, DOI: 10.1021/acsnano.2c1005728https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XivF2isLfO&md5=32a48faf6fc4cdd7ab1eed431b6fd2caCold Nanozyme for Precise Enzymatic Antitumor ImmunityZou, Yuyan; Jin, Bowen; Li, Hui; Wu, Xianbo; Liu, Yihong; Zhao, Henan; Zhong, Da; Wang, Long; Chen, Wansong; Wen, Mei; Liu, You-NianACS Nano (2022), 16 (12), 21491-21504CODEN: ANCAC3; ISSN:1936-0851. (American Chemical Society)Precise catalysis is pursued for the biomedical applications of artificial enzymes. It is feasible to precisely control the catalysis of artificial enzymes via tunning the temp.-dependent enzymic kinetics. The safety window of cold temps. (4-37°C) for the human body is much wider than that of thermal temps. (37-42°C). Although the development of cold-activated artificial enzymes is promising, there is currently a lack of suitable candidates. Herein, a cold-activated artificial enzyme is presented with Bi2Fe4O9 nanosheets (NSs) as a paradigm. The as-obtained Bi2Fe4O9 NSs possess glutathione oxidase (GSHOx)-like activity under cold temp. due to their pyroelectricity. Bi2Fe4O9 NSs trigger the cold-enzymic death of tumor cells via apoptosis and ferroptosis, and minimize the off-target toxicity to normal tissues. Moreover, an interventional device is fabricated to intelligently and remotely control the enzymic activity of Bi2Fe4O9 NSs on a smartphone. With Bi2Fe4O9 NSs as an in situ vaccine, systemic antitumor immunity is successfully activated to suppress tumor metastasis and relapse. Moreover, blood biochem. anal. and histol. examn. indicate the high biosafety of Bi2Fe4O9 NSs for in vivo applications. This cold nanozyme provides a strategy for cancer vaccines, which can benefit the precise control over catalytic nanomedicines.
- 29James, C. C.; de Bruin, B.; Reek, J. N. H. Transition Metal Catalysis in Living Cells: Progress, Challenges, and Novel Supramolecular Solutions. Angew. Chem., Int. Ed. 2023, 62, e202306645 DOI: 10.1002/anie.20230664529https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXhsVCktrbL&md5=70be85b1bc7a0b959e4ac8a4e6b67729Transition Metal Catalysis in Living Cells: Progress, Challenges, and Novel Supramolecular SolutionsJames, Catriona C.; de Bruin, Bas; Reek, Joost N. H.Angewandte Chemie, International Edition (2023), 62 (41), e202306645CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. The importance of transition metal catalysis is exemplified by its wide range of applications, for example in the synthesis of chems., natural products, and pharmaceuticals. However, one relatively new application is for carrying out new-to-nature reactions inside living cells. The complex environment of a living cell is not welcoming to transition metal catalysts, as a diverse range of biol. components have the potential to inhibit or deactivate the catalyst. Here we review the current progress in the field of transition metal catalysis, and evaluation of catalysis efficiency in living cells and under biol. (relevant) conditions. Catalyst poisoning is a ubiquitous problem in this field, and we propose that future research into the development of phys. and kinetic protection strategies may provide a route to improve the reactivity of catalysts in cells.
- 30Hu, C.; Man, R.; Li, H.; Xia, M.; Yu, Z.; Tang, B. Near-Infrared Triggered Self-Accelerating Nanozyme Camouflaged with a Cancer Cell Membrane for Precise Targeted Imaging and Enhanced Cancer Immunotherapy. Anal. Chem. 2023, 95, 13575– 13585, DOI: 10.1021/acs.analchem.3c02218There is no corresponding record for this reference.
- 31Gong, J.; Liu, Q.; Cai, L.; Yang, Q.; Tong, Y.; Chen, X.; Kotha, S.; Mao, X.; He, W. Multimechanism Collaborative Superior Antioxidant CDzymes To Alleviate Salt Stress-Induced Oxidative Damage in Plant Growth. ACS Sustainable Chem. Eng. 2023, 11, 4237– 4247, DOI: 10.1021/acssuschemeng.2c0737131https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXjslKrtLc%253D&md5=66e469f09c04f95a7e51027f7124f813Multimechanism Collaborative Superior Antioxidant CDzymes To Alleviate Salt Stress-Induced Oxidative Damage in Plant GrowthGong, Jiawen; Liu, Quan; Cai, Linlin; Yang, Qi; Tong, Yuping; Chen, Xi; Kotha, Sumasri; Mao, Xiaobo; He, WeiweiACS Sustainable Chemistry & Engineering (2023), 11 (10), 4237-4247CODEN: ASCECG; ISSN:2168-0485. (American Chemical Society)Salt stress has become one major environmental challenge threatening global crop yield. Targeting salt-induced oxidative stress, nanozymes with high-efficiency antioxidant activity and good biocompatibility represent an effective way to improve plant salt tolerance. In this study, carbon dot nanozymes (CDzymes) derived from glucose and histidine are designed to alleviate salt-induced oxidative stress in plant growth. The CDzymes are comprehensively characterized to exhibit broad-spectrum antioxidant capability, allowing them to efficiently scavenge reactive oxygen species (.OH, O2-., H2O2), reactive nitrogen species (.NO and ONOO-), and stable free radicals (DPPH., ABTS.+, PTIO.). Due to their unique structure, CDzymes exhibit multiple antioxidant mechanisms involving electron transfer, H atom transfer, and enzyme-like catalytic behavior. CDzymes have good biocompatibility and can help promote the growth of Pisum sativum Linn and Eucommia under salinity. CDzyme treatment can significantly (p < 0.001) relieve salt stress-induced oxidative damage of biol. components (including chlorophyll, proline, carbohydrate, and protein) and redox enzyme activity, which underlies the mechanism of salt-induced plant wilt. This study demonstrates that CDzymes can act as a potential antioxidant to modulate the level of oxidative stress in biol. systems, opening up new avenues for agricultural salt stress management in crops.
- 32Xu, G.; Du, X.; Wang, W.; Qu, Y.; Liu, X.; Zhao, M.; Li, W.; Li, Y. Q. Plasmonic Nanozymes: Leveraging Localized Surface Plasmon Resonance to Boost the Enzyme-Mimicking Activity of Nanomaterials. Small 2022, 18, 2204131, DOI: 10.1002/smll.20220413132https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XisFWrtrnP&md5=406fb3699800e814e333f34998305e2aPlasmonic Nanozymes: Leveraging Localized Surface Plasmon Resonance to Boost the Enzyme-Mimicking Activity of NanomaterialsXu, Guopeng; Du, Xuancheng; Wang, Weijie; Qu, Yuanyuan; Liu, Xiangdong; Zhao, Mingwen; Li, Weifeng; Li, Yong-QiangSmall (2022), 18 (49), 2204131CODEN: SMALBC; ISSN:1613-6810. (Wiley-VCH Verlag GmbH & Co. KGaA)A review. Nanozymes, a type of nanomaterials that function similarly to natural enzymes, receive extensive attention in biomedical fields. However, the widespread applications of nanozymes are greatly plagued by their unsatisfactory enzyme-mimicking activity. Localized surface plasmon resonance (LSPR), a nanoscale phys. phenomenon described as the collective oscillation of surface free electrons in plasmonic nanoparticles under light irradn., offers a robust universal paradigm to boost the catalytic performance of nanozymes. Plasmonic nanozymes (PNzymes) with elevated enzyme-mimicking activity by leveraging LSPR, emerge and provide unprecedented opportunities for biocatalysis. In this review, the phys. mechanisms behind PNzymes are thoroughly revealed including near-field enhancement, hot carriers, and the photothermal effect. The rational design and applications of PNzymes in biosensing, cancer therapy, and bacterial infections elimination are systematically introduced. Current challenges and further perspectives of PNzymes are also summarized and discussed to stimulate their clin. translation. It is hoped that this review can attract more researchers to further advance the promising field of PNzymes and open up a new avenue for optimizing the enzyme-mimicking activity of nanozymes to create superior nanocatalysts for biomedical applications.
- 33He, T.; Jiang, C.; He, J.; Zhang, Y.; He, G.; Wu, J.; Lin, J.; Zhou, X.; Huang, P. Manganese-Dioxide-Coating-Instructed Plasmonic Modulation of Gold Nanorods for Activatable Duplex-Imaging-Guided NIR-II Photothermal-Chemodynamic Therapy. Adv. Mater. 2021, 33, 2008540, DOI: 10.1002/adma.20200854033https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXlsVynur4%253D&md5=b9a15a18a8f3939c590ce71f0e484ac5Manganese-Dioxide-Coating-Instructed Plasmonic Modulation of Gold Nanorods for Activatable Duplex-Imaging-Guided NIR-II Photothermal-Chemodynamic TherapyHe, Ting; Jiang, Chao; He, Jin; Zhang, Yifan; He, Gang; Wu, Jiayingzi; Lin, Jing; Zhou, Xin; Huang, PengAdvanced Materials (Weinheim, Germany) (2021), 33 (13), 2008540CODEN: ADVMEW; ISSN:0935-9648. (Wiley-VCH Verlag GmbH & Co. KGaA)Nanotheranostic agents of gold nanomaterials in the second near-IR (NIR-II) window have attracted significant attention in cancer management, owing to the reduced background signal and deeper penetration depth in tissues. However, it is still challenging to modulate the localized surface plasmon resonance (LSPR) of gold nanomaterials from the first near-IR (NIR-I) to NIR-II region. Herein, a plasmonic modulation strategy of gold nanorods (GNRs) through manganese dioxide coating is developed for NIR-II photoacoustic/magnetic resonance (MR) duplex-imaging-guided NIR-II photothermal chemodynamic therapy. GNRs are coated with silica dioxide (SiO2) and then covered with magnesium dioxide (MnO2) to obtain the final product of GNR@SiO2@MnO2 (denoted as GSM). The LSPR peak of GNRs could be tuned by adjusting the thickness of the MnO2 layer. Theor. simulations reveal that this plasmonic modulation is mainly due to the change of refraction index around the GNRs after coating with the MnO2 layer. Addnl., the MnO2 layer is demonstrated to degrade into Mn2+ ions in response to peroxide and acidic protons in the tumor microenvironment, which allows for MR imaging and chemodynamic therapy. This plasmonic modulation strategy can be adapted to other metal nanomaterials and the construction of a new class of NIR-II nanotheranostics.
- 34Ye, J.; Lv, W.; Li, C.; Liu, S.; Yang, X.; Zhang, J.; Wang, C.; Xu, J.; Jin, G.; Li, B.; Fu, Y.; Liang, X. Tumor Response and NIR-II Photonic Thermal Co-Enhanced Catalytic Therapy Based on Single-Atom Manganese Nanozyme. Adv. Funct. Mater. 2022, 32, 2206157, DOI: 10.1002/adfm.20220615734https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XisVansbjJ&md5=5efeffd7e5b8521e28e0d569e718762aTumor Response and NIR-II Photonic Thermal Co-Enhanced Catalytic Therapy Based on Single-Atom Manganese NanozymeYe, Jin; Lv, Wubin; Li, Chunsheng; Liu, Shuang; Yang, Xing; Zhang, Jiangwei; Wang, Chen; Xu, Jiating; Jin, Guanqiao; Li, Bin; Fu, Yujie; Liang, XinqiangAdvanced Functional Materials (2022), 32 (47), 2206157CODEN: AFMDC6; ISSN:1616-301X. (Wiley-VCH Verlag GmbH & Co. KGaA)Single-atom nanozymes (SAzymes) can effectively mimic the metal active centers of natural enzymes at the at. level owing to their atomically dispersed active sites, thereby maximizing atom utilization efficiency and d. of active sites. Hence, SAzymes can be considered the most promising candidates to replace natural enzymes. Herein, a PEGylated mesoporous Mn-based single-atom nanozyme (PmMn/SAE) employing a coordination-assisted polymn. pyrolysis strategy that uses polydopamine for photothermal-augmented nanocatalytic therapy is designed. PmMn/SAE exhibits excellent multiple enzymic performance, including catalase-like, oxidase-like, and peroxidase (POD)-like performance, due to the atomically dispersed Mn active species. As a result, PmMn/SAE not only catalyzes the decompn. of endogenous H2O2 to generate O2 for relieving hypoxia inside the tumor but also transfers electrons to O2 to produce superoxide radicals to kill tumor cells. Meanwhile, PmMn/SAE is able to trigger Fenton-like reactions to generate highly toxic hydroxyl radicals to induce cancer cell apoptosis. The POD-like catalytic mechanism of mMn/SAE is revealed using exptl. results and d. functional theory. Furthermor, PmMn/SAE shows good photothermal conversion efficiency (η = 22.1%) in the second near-IR region (1064 nm). Both the in vitro and in vivo exptl. results indicate that PmMn/SAE can effectively kill cancer cells through photothermal-enhanced catalytic therapy.
- 35An, L.; Wang, C.; Tian, Q.; Tao, C.; Xue, F.; Yang, S.; Zhou, X.; Chen, X.; Huang, G. NIR-II laser-mediated photo-Fenton-like reaction via plasmonic Cu9S8 for immunotherapy enhancement. Nano Today 2022, 43, 101397, DOI: 10.1016/j.nantod.2022.10139735https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB38XhtFKksbvO&md5=9e857951fb701bbf746754e7291017bcNIR-II laser-mediated photo-Fenton-like reaction via plasmonic Cu9S8 for immunotherapy enhancementAn, Lu; Wang, Chengbin; Tian, Qiwei; Tao, Cheng; Xue, Fengfeng; Yang, Shiping; Zhou, Xuesu; Chen, Xiaoyuan; Huang, GangNano Today (2022), 43 (), 101397CODEN: NTAOCG; ISSN:1748-0132. (Elsevier Ltd.)Chemodynamic therapy (CDT) is typically used to modulate the immunogenic tumor microenvironment and extend the benefits of immune checkpoint therapy because of its good tumor selectivity. However, the poor catalytic efficiency of CDT agents means that it often needs to be combined with other enhancement strategies, such as radiotherapy and photothermal therapy with high power d., which can inevitably traumatize normal tissues. To overcome these limitations, a near-IR (NIR)-II laser-mediated photo-Fenton-like reaction based on a plasmonic self-doped semiconductor was proposed as a mild enhancement strategy to enhance the immune responses. Exptl. simulations and results of plasmonic Cu9S8 show that the NIR-II laser can enhance the CDT effect based on the plasmon-driven photoredox chem. without inducing a photothermal effect. Furthermore, the enhanced CDT effectively induces immunogenic cell death and dendritic cell maturation both in vitro and in vivo. In addn., the antitumor immune response is greatly enhanced by the synergistic effect of the NIR-II laser in enhancing both CDT and anti-PD-L1. This allows for primary tumor elimination and the effective suppression of distant tumors and lung metastases. Our proposed design indicates that the NIR-II photo-Fenton-like reaction based on the plasmonic semiconductor effectively enhances CDT, thus selectively enhancing immunotherapy.
- 36Li, S.; Shang, L.; Xu, B.; Wang, S.; Gu, K.; Wu, Q.; Sun, Y.; Zhang, Q.; Yang, H.; Zhang, F.; Gu, L.; Zhang, T.; Liu, H. A Nanozyme with Photo-Enhanced Dual Enzyme-Like Activities for Deep Pancreatic Cancer Therapy. Angew. Chem., Int. Ed. 2019, 58, 12624– 12631, DOI: 10.1002/anie.20190475136https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1MXhsFSrt7bJ&md5=c682101dc0351d49ad5ab1c3951d6877A nanozyme with photo-enhanced dual enzyme-like activities for deep pancreatic cancer therapyLi, Shanshan; Shang, Lu; Xu, Bolong; Wang, Shunhao; Gu, Kai; Wu, Qingyuan; Sun, Yun; Zhang, Qinghua; Yang, Hailong; Zhang, Fengrong; Gu, Lin; Zhang, Tierui; Liu, HuiyuAngewandte Chemie, International Edition (2019), 58 (36), 12624-12631CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)Nanozymes have attracted extensive interest owing to their high stability, low cost and easy prepn., esp. in the field of cancer therapy. However, the relatively low catalytic activity of nanozymes in the tumor microenvironment (TME) has limited their applications. Herein, we report a novel nanozyme (PtFe@Fe3O4) with dual enzyme-like activities for highly efficient tumor catalytic therapy. PtFe@Fe3O4 shows the intrinsic photothermal effect as well as photo-enhanced peroxidase-like and catalase-like activities in the acidic TME, thereby effectively killing tumor cells and overcoming the tumor hypoxia. Importantly, a possible photo-enhanced synergistic catalytic mechanism of PtFe@Fe3O4 was first disclosed. We believe that this work will advance the development of nanozymes in tumor catalytic therapy.
- 37Meng, X.; Sun, S.; Gong, C.; Yang, J.; Yang, Z.; Zhang, X.; Dong, H. Ag-Doped Metal-Organic Frameworks’ Heterostructure for Sonodynamic Therapy of Deep-Seated Cancer and Bacterial Infection. ACS Nano 2023, 17, 1174– 1186, DOI: 10.1021/acsnano.2c08687There is no corresponding record for this reference.
- 38Oh, W. D.; Lok, L. W.; Veksha, A.; Giannis, A.; Lim, T. T. Enhanced photocatalytic degradation of bisphenol A with Ag-decorated S-doped g-C3N4 under solar irradiation: Performance and mechanistic studies. Chem. Eng. J. 2018, 333, 739– 749, DOI: 10.1016/j.cej.2017.09.18238https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXhslOis7bJ&md5=25d3315cccece80c10442b8c9ffe8c66Enhanced photocatalytic degradation of bisphenol A with Ag-decorated S-doped g-C3N4 under solar irradiation: Performance and mechanistic studiesOh, Wen-Da; Lok, Li-Wen; Veksha, Andrei; Giannis, Apostolos; Lim, Teik-ThyeChemical Engineering Journal (Amsterdam, Netherlands) (2018), 333 (), 739-749CODEN: CMEJAJ; ISSN:1385-8947. (Elsevier B.V.)Ag-decorated S-doped g-C3N4 composites with different % wt./wt. Ag were synthesized via chem. redn. method. The Ag/S-doped g-C3N4 composites were used as photocatalysts for aq. bisphenol A (BPA) degrdn. under solar irradn. Investigation of the photocatalysts using various characterization methods including X-ray diffractometry, SEM and transmission electron microscopy indicated that the Ag nanoparticles (av. size = 10-20 nm) were well-cryst. and uniformly distributed on the S-doped g-C3N4 (SCN) surface. The photocatalytic performance of SCN was ∼3 times more efficient than that of the g-C3N4, while the Ag/SCN with 12% wt./wt. Ag (Ag-SCN-12) exhibited the highest photocatalytic activity for BPA degrdn. followed by 8% wt./wt. Ag/SCN, 4% wt./wt. Ag/SCN, SCN, and Ag. The effects of pH and Ag-SCN-12 loading on photocatalytic BPA degrdn. were also investigated. The results showed that the Ag-SCN-12 was highly stable (<40 μg L-1 Ag leaching) and could be reused for at least 4 cycles without significant deterioration to its catalytic activity. The incorporation of Ag into the SCN enhanced the photocatalytic activity of SCN due to the improved electron-hole pair sepn. and decreased electron-hole pair recombination rate as evidenced by the photoluminescence emission study. The predominant reactive oxygen species (ROS) generated by the Ag-SCN-12 photocatalytic system was O·-2 which formed secondary ROS (·OH, and 1O2) for BPA degrdn. The mechanism of ROS generation during the photocatalytic process is also proposed. Based on the BPA degrdn. intermediates identified using the LC/MS/MS, the BPA degrdn. pathways in the photocatalytic system are elucidated.
- 39Wang, N.; Li, P.; Zhao, J.; Liu, Y.; Hu, X.; Ling, D.; Li, F. An anisotropic photocatalytic agent elicits robust photoimmunotherapy through plasmonic catalysis-mediated tumor microenvironment modulation. Nano Today 2023, 50, 101827, DOI: 10.1016/j.nantod.2023.101827There is no corresponding record for this reference.
- 40Hasan, A. A.; Kalinina, E.; Tatarskiy, V.; Shtil, A. The Thioredoxin System of Mammalian Cells and Its Modulators. Biomedicines 2022, 10, 1757, DOI: 10.3390/biomedicines10071757There is no corresponding record for this reference.
- 41Zeisel, L.; Felber, J. G.; Scholzen, K. C.; Poczka, L.; Cheff, D.; Maier, M. S.; Cheng, Q.; Shen, M.; Hall, M. D.; Arnér, E. S. J.; Thorn-Seshold, J.; Thorn-Seshold, O. Selective cellular probes for mammalian thioredoxin reductase TrxR1: Rational design of RX1, a modular 1,2-thiaselenane redox probe. Chem. 2022, 8, 1493– 1517, DOI: 10.1016/j.chempr.2022.03.010There is no corresponding record for this reference.
- 42Srivastava, M.; Singh, S.; Self, W. T. Exposure to Silver Nanoparticles Inhibits Selenoprotein Synthesis and the Activity of Thioredoxin Reductase. Environ. Health Perspect. 2012, 120, 56– 61, DOI: 10.1289/ehp.1103928There is no corresponding record for this reference.
- 43Pang, M.; Zeng, H. C. Highly Ordered Self-Assemblies of Submicrometer Cu2O Spheres and Their Hollow Chalcogenide Derivatives. Langmuir 2010, 26, 5963– 5970, DOI: 10.1021/la904292t43https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXisFGnu7g%253D&md5=e436544f3d9b416eeea4d1152bf3c33eHighly Ordered Self-Assemblies of Submicrometer Cu2O Spheres and Their Hollow Chalcogenide DerivativesPang, Maolin; Zeng, Hua ChunLangmuir (2010), 26 (8), 5963-5970CODEN: LANGD5; ISSN:0743-7463. (American Chemical Society)Highly ordered superlattices assembled from transition metal oxide/sulfide submicrometer particles are difficult to prep. due to lack of monodisperse primary building blocks. In this work, we have successfully synthesized monodisperse Cu2O spheres with diams. in the submicrometer regime of 130-135 nm. Using the as-prepd. Cu2O spheres as solid precursor, uniform hollow CuS and CuSe derivs. have also been synthesized in soln. media. More importantly, a range of two-dimensional and three-dimensional superlattices of Cu2O, CuS, and CuSe solid/hollow spheres have been assembled for the first time. Without assistance of conventional sacrificing solid templates, the degree of ordering achieved in these superlattices is comparable to those reported for well-studied silica and polystyrene beads. The realization of these self-assembled superlattices may provide a new way of thin film design and fabrication for this class of photosensitive semiconducting materials using their prefabricated building blocks.
- 44Mao, Z.; Yang, Z.; Tao, W.; Tang, Q.; Xiao, Y.; Jiang, Y.; Guo, S. Ultrafine Ag Nanoparticles Anchored on Hollow S-Doped CeO2 Spheres for Synergistically Enhanced Tetracycline Degradation under Visible Light. Ind. Eng. Chem. Res. 2022, 61, 17092– 17101, DOI: 10.1021/acs.iecr.2c02674There is no corresponding record for this reference.
- 45Guo, Y.; Wang, H.; Ma, X.; Jin, J.; Ji, W.; Wang, X.; Song, W.; Zhao, B.; He, C. Fabrication of Ag-Cu2O/Reduced Graphene Oxide Nanocomposites as Surface-Enhanced Raman Scattering Substrates for in Situ Monitoring of Peroxidase-Like Catalytic Reaction and Biosensing. ACS Appl. Mater. Interfaces 2017, 9, 19074– 19081, DOI: 10.1021/acsami.7b0214945https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXns1OnsrY%253D&md5=37b758771fd78dec577f66fa42c48febFabrication of Ag-Cu2O/Reduced Graphene Oxide Nanocomposites as Surface-Enhanced Raman Scattering Substrates for in Situ Monitoring of Peroxidase-Like Catalytic Reaction and BiosensingGuo, Yue; Wang, Hai; Ma, Xiaowei; Jin, Jing; Ji, Wei; Wang, Xu; Song, Wei; Zhao, Bing; He, ChengyanACS Applied Materials & Interfaces (2017), 9 (22), 19074-19081CODEN: AAMICK; ISSN:1944-8244. (American Chemical Society)Highly sensitive biosensors are essential in medical diagnostics, esp. for monitoring the state of an individual's disease. An ideal way to achieve this objective is to analyze human sweat secretions by non-invasive monitoring. Due to low concns. of target analytes in human secretions, fabrication of ultra-sensitive detection devices is a great challenge. In this work, Ag-Cu2O/reduced graphene oxide (rGO) nanocomposites are prepd. by a facile two-step in situ redn. procedure at room temp. Ag-Cu2O/rGO nanocomposites possess intrinsic peroxidase-like activity and rapidly catalyze oxidn. of the peroxidase substrate 3, 3', 5, 5'-tetramethylbenzidine (TMB) in the presence of H2O2. On the basis of the excellent SERS properties and high peroxidase-like activity of the Ag-Cu2O/rGO nanocomposites, the catalytic oxidn. of TMB can be monitored by SERS. This approach can detect H2O2 and glucose with high sensitivity and distinguish between diabetic and normal individuals using glucose levels in fingerprints. Our work provides direction for designing other SERS substrates with high catalytic activity and the potential for application in biosensing, forensic investigation, and medical diagnostics.
- 46Rasheed, M.; Saira, F.; Batool, Z.; khan, H. M.; Yaseen, J.; Arshad, M.; Kalsoom, A.; Ahmeda, H. E.; Naeem Ashiq, M. N. Facile synthesis of a CuSe/PVP nanocomposite for ultrasensitive non-enzymatic glucose biosensing. RSC Adv. 2023, 13, 26755– 26765, DOI: 10.1039/d3ra03175fThere is no corresponding record for this reference.
- 47Kayed, K.; Mayada Issa, M.; Al-ourabi, H. The FTIR spectra of Ag/Ag2O composites doped with silver nanoparticles. J. Exp. Nanosci. 2024, 19, 2336227, DOI: 10.1080/17458080.2024.2336227There is no corresponding record for this reference.
- 48Abu-Elsaad, N. I.; Nawara, A. S.; Mazen, S. A. Synthesis, structural characterization, and magnetic properties of Ni-Zn nanoferrites substituted with different metal ions (Mn2+, Co2+, and Cu2+). J. Phys. Chem. Solids 2020, 146, 109620, DOI: 10.1016/j.jpcs.2020.109620There is no corresponding record for this reference.
- 49Khurana, A.; Tekula, S.; Saifi, M. A.; Venkatesh, P.; Godugu, C. Therapeutic applications of selenium nanoparticles. Pharmacother. 2019, 111, 802– 812, DOI: 10.1016/j.biopha.2018.12.146There is no corresponding record for this reference.
- 50Zhang, X. L.; Hu, S. J.; Zheng, Y. R.; Wu, R.; Gao, F. Y.; Yang, P. P.; Niu, Z. Z.; Gu, C.; Yu, X.; Zheng, X. S.; Ma, C.; Zheng, X.; Zhu, J. F.; Gao, M. R.; Yu, S. H. Polymorphic cobalt diselenide as extremely stable electrocatalyst in acidic media via a phase-mixing strategy. Nat. Commun. 2019, 10, 5338, DOI: 10.1038/s41467-019-12992-y50https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BB3Mfjt1aisw%253D%253D&md5=5bc60ba5d2d1645d89b95f8ddb9066f6Polymorphic cobalt diselenide as extremely stable electrocatalyst in acidic media via a phase-mixing strategyZhang Xiao-Long; Zheng Ya-Rong; Wu Rui; Gao Fei-Yue; Yang Peng-Peng; Niu Zhuang-Zhuang; Gu Chao; Yu Xingxing; Gao Min-Rui; Yu Shu-Hong; Hu Shao-Jin; Zheng Xiao; Zheng Xu-Sheng; Zhu Jun-Fa; Ma Cheng; Yu Shu-HongNature communications (2019), 10 (1), 5338 ISSN:.Many platinum group metal-free inorganic catalysts have demonstrated high intrinsic activity for diverse important electrode reactions, but their practical use often suffers from undesirable structural degradation and hence poor stability, especially in acidic media. We report here an alkali-heating synthesis to achieve phase-mixed cobalt diselenide material with nearly homogeneous distribution of cubic and orthorhombic phases. Using water electroreduction as a model reaction, we observe that the phase-mixed cobalt diselenide reaches the current density of 10 milliamperes per square centimeter at overpotential of mere 124 millivolts in acidic electrolyte. The catalyst shows no sign of deactivation after more than 400 h of continuous operation and the polarization curve is well retained after 50,000 potential cycles. Experimental and computational investigations uncover a boosted covalency between Co and Se atoms resulting from the phase mixture, which substantially enhances the lattice robustness and thereby the material stability. The findings provide promising design strategy for long-lived catalysts in acid through crystal phase engineering.
- 51Yang, C.; Wang, M.; Chang, M.; Yuan, M.; Zhang, W.; Tan, J.; Ding, B.; Ma, P. a.; Lin, J. Heterostructural Nanoadjuvant CuSe/CoSe2 for Potentiating Ferroptosis and Photoimmunotherapy through Intratumoral Blocked Lactate Efflux. J. Am. Chem. Soc. 2023, 145, 7205– 7217, DOI: 10.1021/jacs.2c1277251https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3sXlvVOhsLs%253D&md5=730aaa576b690335b0b061a70b01afa9Heterostructural Nanoadjuvant CuSe/CoSe2 for Potentiating Ferroptosis and Photoimmunotherapy through Intratumoral Blocked Lactate EffluxYang, Chunzheng; Wang, Man; Chang, Mengyu; Yuan, Meng; Zhang, Wenying; Tan, Jia; Ding, Binbin; Ma, Ping'an; Lin, JunJournal of the American Chemical Society (2023), 145 (13), 7205-7217CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)The desirable curative effect in clin. immunotherapy has been challenging due to the immunosuppressive tumor microenvironment (TME) with high lactic acid (LA) metab. in solid tumors. Although targeting metabolic reprogramming of tumor cells can restore the survival and function of immune cells in the TME, it is also plagued by insufficient immunogenicity. Herein, an activatable immunomodulatory nanoadjuvant CuSe/CoSe2@syrosingopine (CSC@Syro) is constructed for simultaneously relieving immunosuppressive TME and boosting tumor immune response. Specifically, CuSe/CoSe2 (CSC) exhibits TME-activated glutathione (GSH) depletion and hydroxyl radical (•OH) generation for potential ferroptosis. Meanwhile, the remarkable photothermal conversion efficiency and elevated photocatalytic ROS level both promote CSC heterostructures to induce robust immunogenic cell death (ICD). Besides, the loaded syrosingopine inhibitor achieves LA metab. blockade in cancer cells by downregulating the expression of monocarboxylate transporter 4 (MCT4), which could sensitize ferroptosis by intracellular milieu acidification and neutralize the acidic TME to alleviate immunosuppression. Hence, advanced metabolic modulation confers the potentiated immune infiltration of ICD-stimulated T lymphocytes and further reinforces antitumor therapy. In brief, CSC@Syro-mediated synergistic therapy could elicit potent immunogenicity and suppress tumor proliferation and metastasis effectually by integrating the tumor metabolic regulation and ferroptosis with immunotherapy.
- 52Ji, R.; Sun, W.; Chu, Y. One-step hydrothermal synthesis of Ag/Cu2O heterogeneous nanostructures over Cu foil and their SERS applications. RSC Adv. 2014, 4, 6055– 6059, DOI: 10.1039/c3ra44281k52https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXls1WgsA%253D%253D&md5=c866d55f6b19a4a48bb0b83390eea95eOne-step hydrothermal synthesis of Ag/Cu2O heterogeneous nanostructures over Cu foil and their SERS applicationsJi, Ran; Sun, Wendong; Chu, YingRSC Advances (2014), 4 (12), 6055-6059CODEN: RSCACL; ISSN:2046-2069. (Royal Society of Chemistry)In this paper, Ag/Cu2O heterogeneous nanostructured films (HNFs) were prepd. by a one-step hydrothermal method. It involved only two materials, AgNO3 and Cu foil, in the aq. soln. to form Ag/Cu2O HNF. X-ray diffraction (XRD), XPS, energy dispersive x-ray spectroscopy (EDX), SEM (SEM), transmission electron microscopy (TEM) and high-resoln. transmission electron microscopy (HRTEM) were used to characterize the Ag/Cu2O films. Ag nanoparticles and Cu2O nanocubes were formed by redox reactions and the Ag nanoparticles deposited on the Cu2O nanocubes via electrostatic attraction. The obtained Ag/Cu2O HNF was found to be a good candidate for SERS application.
- 53Liu, J.; Zhang, X.; Wen, B.; Li, Y.; Wu, J.; Wang, Z.; Wu, T.; Zhao, R.; Yang, S. Pre-carbonized nitrogen-rich polytriazines for the controlled growth of silver nanoparticles: catalysts for enhanced CO2 chemical conversion at atmospheric pressure. Catal. Sci. Technol. 2021, 11, 3119– 3127, DOI: 10.1039/D0CY02473B53https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3MXlt1aks7c%253D&md5=a37325413de88843ab6fc12d2fb04b4cPre-carbonized nitrogen-rich polytriazines for the controlled growth of silver nanoparticles: catalysts for enhanced CO2 chemical conversion at atmospheric pressureLiu, Jian; Zhang, Xiaoyi; Wen, Bingyan; Li, Yipei; Wu, Jingjing; Wang, Zhipeng; Wu, Ting; Zhao, Rusong; Yang, ShenghongCatalysis Science & Technology (2021), 11 (9), 3119-3127CODEN: CSTAGD; ISSN:2044-4753. (Royal Society of Chemistry)High catalytic activity and sufficient durability are two unavoidable key indexes of an efficient heterogeneous catalyst for the direct carboxylation of terminal alkynes with CO2 conversion. Nitrogen-rich covalent triazine frameworks (CTFs) are promising substrates, while random distribution of some residual -NH2 groups brings challenges to the controlled growth of catalytic species. Here, we adopt a pre-carbonization protocol, annealing below the carbonization temp., to eliminate the random -NH2 groups in CTFs and meanwhile to promote polycondensation degree under the premise of maintaining the pore structure. Benefiting from the improved condensation and orderly N atoms, p-CTF-250, for which CTFs are annealed at 250°C, exhibits improved CO2 adsorption capacity and the ability to control the growth of Ag NPs. Mono-dispersed Ag NPs are generated controllably and entrapped to form Ag@p-CTF-250 catalysts. These Ag@p-CTF-250 catalysts were employed in the direct carboxylation of various terminal alkynes with CO2 under mild conditions (50°C, 1 atm) and showed excellent catalytic activity. In addn., these catalysts have robust recyclability and can be used for at least 5 catalytic runs while retaining yield above 90%. CO2 conversion proceeds well under the synergistic effect between the high CO2 capture capability and the uniform tiny Ag NPs in Ag@p-CTF-250 "nanoreactors". The results represent an efficient strategy for controlling the growth of metallic nanoparticles in porous org. polymer substrates contg. disordered heteroatoms.
- 54Yu, B.; Zhou, Y.; Li, P.; Tu, W.; Li, P.; Tang, L.; Ye, J.; Zou, Z. Photocatalytic reduction of CO2 over Ag/TiO2 nanocomposites prepared with a simple and rapid silver mirror method. Nanoscale 2016, 8, 11870– 11874, DOI: 10.1039/C6NR02547A54https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XnvFOitbc%253D&md5=6b6f70710d765bcc3e55734dc2364c48Photocatalytic reduction of CO2 over Ag/TiO2 nanocomposites prepared with a simple and rapid silver mirror methodYu, Bingcheng; Zhou, Yong; Li, Peng; Tu, Wenguang; Li, Ping; Tang, Lanqin; Ye, Jinhua; Zou, ZhigangNanoscale (2016), 8 (23), 11870-11874CODEN: NANOHL; ISSN:2040-3372. (Royal Society of Chemistry)The photocatalytic redn. of CO2 over Ag/TiO2 composites prepd. with a simple silver mirror reaction method was investigated under UV-visible irradn. in both gas-phase (CO2 + water vapor) and aq. soln. (CO2-satd. NaHCO3 soln.) systems. The as-prepd. Ag/TiO2 nanocomposite exhibits efficient photocatalytic activity due to the surface plasmonic resonance and electron sink effect of the Ag component, which was found to be closely related to the size and loading amt. of Ag. The rapid silver method is effective at curbing the size of Ag, so photocatalytic activity can be improved. Diverse org. chem. products were detected, including mainly methane and methanol as well as a small amt. of C2 and C3 species such as acetaldehyde and acetone. Possible photocatalytic mechanisms were proposed. This artificial photosynthesis process may give a prosperous route to the removal of CO2 while simultaneously converting CO2 to valuable fuels based on highly efficient photocatalysts.
- 55Sathishkumar, K.; Sowmiya, K.; Arul Pragasan, L.; Rajagopal, R.; Sathya, R.; Ragupathy, S.; Krishnakumar, M.; Minnam Reddy, V. R. Enhanced photocatalytic degradation of organic pollutants by Ag-TiO2 loaded cassava stem activated carbon under sunlight irradiation. Chemosphere 2022, 302, 134844, DOI: 10.1016/j.chemosphere.2022.134844There is no corresponding record for this reference.
- 56Wang, C.; Cao, F. J.; Ruan, Y.; Jia, X.; Zhen, W.; Jiang, X. Specific Generation of Singlet Oxygen through the Russell Mechanism in Hypoxic Tumors and GSH Depletion by Cu-TCPP Nanosheets for Cancer Therapy. Angew. Chem. 2019, 131, 9951– 9955, DOI: 10.1002/ange.201903981There is no corresponding record for this reference.
- 57Chiang, C.; Chu, K.; Lin, C.; Xie, S.; Liu, Y.; Demeshko, S.; Lee, G.; Meyer, F.; Tsai, M.; Chiang, M.; Chien-Ming Lee, C. Photoinduced NO and HNO Production from Mononuclear {FeNO}6 Complex Bearing a Pendant Thiol. J. Am. Chem. Soc. 2020, 142, 8649– 8661, DOI: 10.1021/jacs.9b1383757https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BB3cXmvFGhu74%253D&md5=02e22fb6eb688a5eee00349ea9816167Photoinduced NO and HNO production from mononuclear {FeNO}6 complex bearing a pendant thiolChiang, Chuan-Kuei; Chu, Kai-Ti; Lin, Chia-Chin; Xie, Shi-Rou; Liu, Yu-Chiao; Demeshko, Serhiy; Lee, Gene-Hsiang; Meyer, Franc; Tsai, Ming-Li; Chiang, Ming-Hsi; Lee, Chien-MingJournal of the American Chemical Society (2020), 142 (19), 8649-8661CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Light triggers the formation of HNO from a metal-nitrosyl species, facilitated by an intramol. pendant thiol proton. Two {FeNO}6 complexes (the Enemark-Felthan notation), [Fe(NO)(TMSPS2)(TMSPS2H)] (1, TMSPS2H2 = 2,2'-dimercapto-3,3'-bis((trimethylsilyl)diphenyl)phenylphosphine; H is a dissociable proton) with a pendant thiol and [Fe(NO)(TMSPS2)(TMSPS2CH3)] (2) bearing a pendant thioether, are spectroscopically and structurally characterized. Both complexes are highly sensitive to visible light. Upon photolysis, complex 2 undergoes NO dissocn. to yield a mononuclear Fe(III) complex, [Fe(TMSPS2)(TMSPS2CH3)] (3). In contrast, the pendant SH of 1 can act as a trap for the departing NO radical upon irradn., resulting in the formation of an intermediate A with an intramol. [SH···ON-Fe] interaction. As suggested by computational results (d. functional theory), the NO stretching frequency (νNO) is sensitive to the intramol. interaction between the pendant ligand and the iron-bound NO, and a shift of νNO from 1833 (1) to 1823 cm-1 (A) is obsd. exptl. Subsequent photolysis of the intermediate A results in HNO prodn. and a thiyl group that then coordinates to the Fe center for the formation of [Fe(TMSPS2)2] (4). In contrast with the common acid-base coupling pathway, the HNO is not voluntarily yielded from 1 but rather is generated by the photopromoted pathway. The photogenerated HNO can further react with [MnIII(TMSPS3)(DABCO)] TMSPS3H3 = (2,2'2''-trimercapto-3,3',3''-tris(trimethylsilyl)triphenylphosphine; DABCO = 1,4-diazabicyclo[2.2.2]octane) in org. media to yield anionic [Mn(NO)(TMSPS3)]- (5-) with a {MnNO}6 electronic configuration, whereas [MnIII(TMSPS3)(DABCO)] reacts with NO gas for the formation of a {MnNO}5 species, [Mn(NO)(TMSPS3)] (6). Effective differentiation of the formation of HNO from complex 1 with the pendant SH vs. NO from 2 with the pendant SMe is achieved by the employment of [MnIII(TMSPS3)(DABCO)].
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Additional experimental materials, methods, and characterization data for the preparation of CSA and CS and other in vitro and in vivo experimental data (PDF)
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