Chemodynamic therapy holds great potential for cancer treatment due to its reliable curative effects, minimal invasiveness, and few systemic side effects. However, the limited amount of intracellular H₂O₂ makes achieving high-performance chemodynamic therapy challenging. Herein, we report a core-shell nanoplatform with dual-responsive disassembly that self-supplies H₂O₂ and undergoes an autocatalytic Fenton reaction for enhanced chemodynamic therapy. The platform was designed by coating glucose oxidase-mimicking nanozyme gold nanoparticles (AuNPs) with a metal-polyphenol network (Au@MPN). Both ATP and low pH can disassemble the Au@MPN to release Fe(III), which can then be reduced into Fe(II) by the simultaneously released tannic acid (TA). In particular, the exposed AuNPs can catalyze the oxidation of intracellular glucose to produce H₂O₂. Subsequently, Fe(II) and the self-supplied H₂O₂ induce an efficient Fenton reaction for chemodynamic therapy by generating hydroxyl radicals (•OH) that are highly toxic to cancer cells. Moreover, tumor growth can be effectively suppressed after both intratumoral and intravenous Au@MPN administration. Additionally, metastatic melanoma lung tumors could be inhibited by intratracheal instillation of Au@MPN. Thus, this work not only reports a facile method to construct a chemodynamic agent with self-supplied H₂O₂ and high therapeutic efficiency but also provides insight into the design of nanoplatforms with enhanced efficiency for chemodynamic therapy.

化学动力学疗法具有疗效可靠、创伤小、全身副作用少等优点，在癌症治疗中具有巨大潜力。_{然而，细胞内 H 2} O ₂的数量有限使得实现高性能化学动力学疗法具有挑战性。在此，我们报告了一种具有双重响应拆卸的核-壳纳米平台，可自供应 H ₂ O ₂并经历自催化芬顿反应以增强化学动力学治疗。该平台的设计是通过用金属多酚网络 (Au@MPN) 包裹葡萄糖氧化酶模拟纳米酶金纳米粒子 (AuNPs)。ATP 和低 pH 值都可以分解 Au@MPN 以释放 Fe(III)，然后可以通过同时释放的单宁酸 (TA) 将其还原为 Fe(II)。特别是，暴露的 AuNPs 可以催化细胞内葡萄糖氧化产生 H ₂ O ₂。随后，Fe(II) 和自给自足的 H ₂ O ₂通过产生对癌细胞具有高毒性的羟基自由基 (•OH)，诱导用于化学动力学治疗的有效芬顿反应。此外，肿瘤内和静脉内注射 Au@MPN 后均可有效抑制肿瘤生长。此外，转移性黑色素瘤肺肿瘤可以通过气管内滴注 Au@MPN 来抑制。因此，这项工作不仅报告了一种构建具有自供 H ₂ O ₂和高治疗效率的化学动力学试剂的简便方法，而且还提供了对纳米平台设计的深入了解，以提高化学动力学治疗的效率。