This study applies in situ production of hypochlorous acid (HOCl) to improve the therapeutic efficacy of platinum drugs. The phagocytic enzyme myeloperoxidase (MPO) is coated with two functional polyphenol derivatives (platinum prodrug polyphenols and PEG polyphenols) and ferric ion by metal phenolic coordination, which can shield MPO from degradation by other compounds in the blood. Moreover, the platinum prodrug can be reduced to cisplatin in cells and produce hydrogen peroxide (H₂O₂). The MPO catalyzes the conversion of H₂O₂ to HOCl in the intercellular environment. The as-prepared MPO Pt PEG nanoparticles (MPP NPs) can be employed as a reactive oxygen species cascade bioreaction to enhance platinum drug therapy. The MPP NPs show prolonged blood circulation and high tumor accumulation as evidenced by ⁸⁹Zr-based positron emission tomography imaging. The MPP NPs effectively inhibit tumor growth in vivo. As a first-in-class platform to harness the highly toxic HOCl in nanomedicine for cancer therapy, this strategy may open doors for further development of progressive therapeutic systems.

中文翻译：

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次氯酸促进髓过氧化物酶包裹的治疗性金属酚醛纳米粒子对铂类药物的化学治疗

这项研究适用于次氯酸（HOCl）的原位生产，以提高铂类药物的治疗效果。吞噬酶髓过氧化物酶（MPO）通过金属酚配位被两种功能性多酚衍生物（铂前药多酚和PEG多酚）和三价铁离子包被，可以保护MPO免受血液中其他化合物的降解。此外，铂前药可在细胞中还原为顺铂并产生过氧化氢（H ₂ O ₂）。MPO催化H ₂ O ₂的转化到细胞间环境中的HOCl。所制备的MPO Pt PEG纳米颗粒（MPP NPs）可以用作活性氧的级联生物反应，以增强铂类药物治疗。MPP NPs显示出延长的血液循环和较高的肿瘤蓄积，如⁸⁹种基于Zr的正电子发射断层显像所证明的那样。MPP NPs有效抑制体内肿瘤的生长。作为在纳米药物中利用剧毒的HOCl进行癌症治疗的一流平台，该策略可能为进一步开发渐进治疗系统打开大门。