Chemodynamic therapy (CDT) has great potential in cancer treatment, but its efficacy is limited due to non-specificity, insufficient hydrogen peroxide (H₂O₂), and excessive glutathione (GSH) within the tumor microenvironment (TME). Here, an intelligent nanoplatform (Fe₃O₄@MnO₂@NO@Au NPs, abbreviated as ^CD44FMNA) is reported for the treatment of breast cancer, which is constructed with Fe₃O₄ nanoparticles (NPs) as the core coated with manganese dioxide (MnO₂) nanoshells encapsulating NO donors and gold nanoparticles (Au NPs) within the pores of MnO₂, followed by the conjugation of targeting ligand anti-CD44 mAb. The fabricated ^CD44FMNA initially remains inactive in normal cells, but after CD44 receptor -mediated MDA-MB-231 cell-specific endocytosis, acidic TME can induce the decomposition of the MnO₂ shell to release NO donors, thereby dually depleting the existing GSH in cells and enhancing the Fenton-like reaction in a cascade manner. The generation of hydroxyl radicals (·OH) and the dual depletion of GSH can significantly weaken the GSH-related antioxidant defense system (ADS) within MDA-MB-231 cells, accelerating apoptosis and cell death via the mitochondrial pathway. In addition, in vivo studies demonstrate that ^CD44FMNA can effectively inhibit tumor growth with good biosafety. Therefore, this nanoplatform may provide an effective therapy for the treatment of breast cancer.

中文翻译：

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智能一氧化氮 (NO) 产生免疫三金属纳米催化剂触发乳腺癌治疗中的化学动力学疗法

化学动力学疗法（CDT）在癌症治疗中具有巨大潜力，但由于肿瘤微环境（TME）内的非特异性、过氧化氢（H ₂ O ₂ ）不足和谷胱甘肽（GSH）过多，其疗效受到限制。在此，报道了一种用于治疗乳腺癌的智能纳米平台（Fe ₃ O ₄ @MnO ₂ @NO@Au NPs，缩写为^{CD44 FMNA），该平台以Fe} ₃ O ₄纳米颗粒（NPs）为核心构建而成，二氧化锰 (MnO _{2 ) 纳米壳将 NO 供体和金纳米粒子 (Au NP) 封装在 MnO 2}的孔内，然后结合靶向配体抗 CD44 mAb。制备的^{CD44 FMNA 最初在正常细胞中保持无活性，但在 CD44 受体介导的 MDA-MB-231 细胞特异性内吞作用后，酸性 TME 可以诱导 MnO} ₂壳分解，释放 NO 供体，从而双重耗尽细胞中现有的 GSH细胞并以级联方式增强芬顿反应。羟自由基（ · OH）的产生和GSH的双重消耗可以显着削弱MDA-MB-231细胞内GSH相关的抗氧化防御系统（ADS），通过线粒体途径加速细胞凋亡和死亡。此外，体内研究表明^CD44 FMNA可以有效抑制肿瘤生长，具有良好的生物安全性。因此，该纳米平台可能为乳腺癌的治疗提供有效的疗法。