乳腺癌具有较高的发病率和死亡率，是一个重大的全球健康负担。传统的治疗方法——手术、化疗和放疗——被广泛使用，但存在复发、转移和显着副作用（包括损害健康组织）等缺点。为了解决这些限制，正在开发新的治疗策略。过氧化物酶（POD）可以催化肿瘤微环境中过量的H2O2产生活性氧（ROS），其通过破坏氧化还原稳态和调节凋亡相关蛋白来诱导癌细胞凋亡。然而，天然酶面临稳定性差、成本高、对环境条件敏感等挑战，限制了其在乳腺癌治疗中的应用。纳米酶，具有类酶活性的纳米材料，克服了这些限制，提供了一种有前途的替代品。在这项研究中，我们通过在柠檬酸三钠还原法合成的金纳米颗粒（Au NPs）上沉积金属钯，成功制备了具有过氧化物酶活性的Au@Pd纳米酶和抗坏血酸减少。体外验证通过一系列实验进行，包括ROS检测、流式细胞术、CCK-8测定、DNA损伤评估、活/死细胞染色、蛋白质印迹(WB)和qPCR。通过尾静脉注射药物进行肿瘤治疗，随后对治疗组织进行HE染色和血液生化分析。Au@Pd纳米酶可以通过EPR效应在肿瘤部位有效积聚并发挥类似过氧化物酶的活性，催化肿瘤微环境中过量的H2O2产生ROS。这会触发细胞凋亡途径和DNA损伤，导致抗凋亡蛋白Bcl-2下调，促凋亡蛋白Bax上调，诱导凋亡相关基因，表现出强大的抗肿瘤作用。针对乳腺癌细胞治疗的肿瘤微环境的高效纳米酶介导的催化治疗策略。© 2024。作者。

Breast cancer, with its high morbidity and mortality rates, is a significant global health burden. Traditional treatments-surgery, chemotherapy, and radiotherapy-are widely used but come with drawbacks such as recurrence, metastasis, and significant side effects, including damage to healthy tissues. To address these limitations, new therapeutic strategies are being developed. Peroxidases (POD) can catalyze excess H2O2 in the tumor microenvironment to generate reactive oxygen species (ROS), which induce cancer cell apoptosis by disrupting redox homeostasis and modulating apoptosis-related proteins. However, natural enzymes face challenges like poor stability, high cost, and sensitivity to environmental conditions, limiting their application in breast cancer treatment. Nanozymes, nanomaterials with enzyme-like activity, offer a promising alternative by overcoming these limitations.In this study, we successfully prepared Au@Pd nanozymes with peroxidase activity by depositing metallic Pd on Au nanoparticles (Au NPs) synthesized using a trisodium citrate reduction method and ascorbic acid reduction. The in vitro validation was conducted through a series of experiments, including ROS detection, flow cytometry, CCK-8 assay, DNA damage assessment, live/dead cell staining, Western blot (WB), and qPCR. Tumor treatment was performed via tail vein injection of the drug, followed by HE staining of the treated tissues and biochemical analysis of the blood.Au@Pd nanozymes can effectively accumulate at the tumor site through the EPR effect and exert peroxidase-like activity, catalyzing the excess H2O2 in the tumor microenvironment to produce ROS. This triggers apoptosis pathways and DNA damage, leading to the downregulation of the anti-apoptotic protein Bcl-2, upregulation of the pro-apoptotic protein Bax, and induction of apoptosis-related genes, demonstrating strong anti-tumor effects.This study developed an efficient nanozyme-mediated catalytic therapy strategy targeting the tumor microenvironment for the treatment of breast cancer cells.© 2024. The Author(s).