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.
Institute of Clinical Pharmacy, Jining No. 1 People's Hospital, Shandong First Medical University, Jining 272000, Shandong, China.
ACS Biomater Sci Eng. 2024 Aug 12;10(8):5290-5299. doi: 10.1021/acsbiomaterials.4c00929. Epub 2024 Jul 16.
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 (HO) 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 HO, leading to the generation of various ROS including hydroxyl radical (OH), superoxide radicals (O), and singlet oxygen (O), facilitated by the Cu(II)/Cu(I) redox and HO 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.
扰乱恶性肿瘤细胞内的细胞氧化还原稳态，特别是提高活性氧（ROS），是癌症治疗的有效策略之一。基于纳米酶的 ROS 产生为癌症治疗提供了一种很有前途的策略。然而，由于纳米酶的催化活性不足或对过氧化氢（HO）或氧气的高度依赖，其治疗效果受到限制。在此，我们报道了一种基于具有明确结构的 CuSe 空心纳米立方（CS）均匀覆盖有 Ag 纳米颗粒（AgNPs）的纳米酶（CSA），以扰乱细胞氧化还原稳态，并催化级联的细胞内生化反应产生 ROS，用于协同治疗乳腺癌。在该体系中，CSA 可以与硫氧还蛋白还原酶（TrxR）相互作用并耗尽肿瘤微环境激活的谷胱甘肽（GSH），破坏细胞抗氧化防御系统并增加 ROS 的产生。此外，CSA 对 HO 具有高过氧化物酶模拟活性，通过 Cu(II)/Cu(I) 氧化还原和 HO 循环，以及丰富的催化活性金属位点，生成各种 ROS，包括羟基自由基（OH）、超氧自由基（O）和单线态氧（O）。此外，由于 AgNPs 的吸收和电荷分离性能，CSA 在近红外二区（NIR-II，1064nm）具有优异的光热性能，并增强了癌细胞中的光催化 ROS 水平。由于 TrxR 活性的抑制、GSH 的耗竭、CSA 的高过氧化物酶模拟活性以及大量 ROS 的产生，CSA 对肿瘤生长具有显著且特异性的抑制作用。
