The redox homeostasis in tumors enhances their antioxidant defense ability, limiting reactive oxygen species mediated tumor therapy efficacy. The development of strategies for specific and continuous disruption of the redox homeostasis in tumor cells facilitates the improvement of the cancer therapeutic effect by promoting the apoptosis of tumor cells. Herein, a responsively biodegradable targeting multifunctional integrated nanosphere (HDMn-QDs/PEG-FA) is designed to enhance the anti-tumor efficacy by triggering intratumoral cascade reactions to effectively disrupt intracellular redox homeostasis. Once HDMn-QDs/PEG-FA enters tumor cells, manganese dioxide (MnO₂) shell on the surface of nanosphere consumes glutathione (GSH) to produce Mn²⁺, enabling enhanced chemodynamic therapy (CDT) via a Fenton-like reaction and T₁-weighted magnetic resonance imaging. Meanwhile, the degradation of MnO₂ can also cause the fluorescence recovery of quantum dots conjugated on the surface of the shell, realizing “turn-on” fluorescence imaging. In addition, the doxorubicin is released because of the cleavage of the embedded SS bond in the hybrid core framework by GSH. A superior synergistic therapeutic efficiency combined CDT and chemotherapy is shown by HDMn-QDs/PEG-FA in vivo. The tumor-inhibition rate reaches to 94.8% and does not cause normal tissue damage due to the good targeting and tumor microenvironment-specific response.

中文翻译：

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氧化还原失衡引发肿瘤内级联反应，用于肿瘤“开启”成像和协同治疗

肿瘤中的氧化还原稳态增强了它们的抗氧化防御能力，限制了活性氧介导的肿瘤治疗功效。开发特异性和持续破坏肿瘤细胞氧化还原稳态的策略，通过促进肿瘤细胞的凋亡促进癌症治疗效果的提高。在此，一种响应性可生物降解靶向多功能集成纳米球 (HDMn-QDs/PEG-FA) 旨在通过触发瘤内级联反应有效破坏细胞内氧化还原稳态来增强抗肿瘤功效。一旦HDMn-QDs/PEG-FA进入肿瘤细胞，纳米球表面的二氧化锰(MnO _{2 )壳就会消耗谷胱甘肽(GSH)产生Mn} ²⁺，通过类芬顿反应和 T ₁加权磁共振成像实现增强化学动力学治疗 (CDT)。_{同时，MnO 2}的降解还可以引起壳表面共轭量子点的荧光恢复，实现“开启”荧光成像。此外，由于GSH 对混合核心框架中嵌入的 S  S 键的裂解，阿霉素被释放。HDMn-QDs/PEG-FA 在体内显示出结合 CDT 和化学疗法的卓越协同治疗效率。由于良好的靶向性和肿瘤微环境特异性反应，抑瘤率高达94.8%，不会造成正常组织损伤。