扰乱恶性细胞内的细胞氧化还原稳态，特别是改善活性氧（ROS），是癌症治疗的有效策略之一。基于纳米酶的 ROS 生成为癌症治疗提供了一种有前景的策略。然而，由于纳米酶的催化活性不足或对过氧化氢（H2O2）或氧气的高度依赖，其治疗效果受到限制。在此，我们报道了一种纳米酶（CSA），其基于均匀覆盖有银纳米颗粒（AgNP）的明确的CuSe中空纳米立方体（CS），可扰乱细胞氧化还原稳态并催化一系列细胞内生化反应产生ROS，用于乳腺的协同治疗癌症。在该系统中，CSA 可以与硫氧还蛋白还原酶 (TrxR) 相互作用，消耗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 H2O2 具有高过氧化物酶模拟活性，在 Cu(II)/ Cu(I) 氧化还原和 H2O2 循环，以及丰富的催化活性金属位点。此外，由于AgNPs的吸收和电荷分离性能，CSA在第二近红外（NIR-II，1064 nm）区域表现出优异的光热性能，并提高了癌细胞中光催化ROS水平。由于 TrxR 活性的抑制、GSH 的消耗、CSA 的高过氧化物酶模拟活性以及丰富的 ROS 生成，CSA 对肿瘤生长表现出显着且特异性的抑制作用。

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.