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首页> 外文期刊>Advanced Materials >A Metal-Polyphenol-Coordinated Nanomedicine for Synergistic Cascade Cancer Chemotherapy and Chemodynamic Therapy
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A Metal-Polyphenol-Coordinated Nanomedicine for Synergistic Cascade Cancer Chemotherapy and Chemodynamic Therapy

机译：金属-多酚协同纳米药物的协同级联癌症化学疗法和化学动力疗法。

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The clinical application of chemotherapy is impeded by the unsatisfactory efficacy and severe side effects. Chemodynamic therapy (CDT) has emerged as an efficient strategy for cancer treatment utilizing Fenton chemistry to destroy cancer cells by converting endogenous H2O2 into highly toxic reactive oxygen species. Apart from the chemotherapeutic effect, cisplatin is able to act as an artificial enzyme to produce H2O2 for CDT through cascade reactions, thus remarkably improving the anti-tumor outcomes. Herein, an organic theranostic nanomedicine (PTCG NPs) is constructed with high loading capability using epigallocatechin-3-gallate (EGCG), phenolic platinum(IV) prodrug (Pt-OH), and polyphenol modified block copolymer (PEG-b-PPOH) as the building blocks. The high stability of PTCG NPs during circulation stems from their strong metal-polyphenol coordination interactions, and efficient drug release is realized after cellular internalization. The activated cisplatin elevates the intracellular H2O2 level through cascade reactions. This is further utilized to produce highly toxic reactive oxygen species catalyzed by an iron-based Fenton reaction. In vitro and in vivo investigations demonstrate that the combination of chemotherapy and chemodynamic therapy achieves excellent anticancer efficacy. Meanwhile, systemic toxicity faced by platinum-based drugs is avoided through this nanoformulation. This work provides a promising strategy to develop advanced nanomedicine for cascade cancer therapy.
机译：疗效不佳和严重的副作用阻碍了化学疗法的临床应用。化学动力疗法（CDT）已经成为一种有效的癌症治疗策略，利用Fenton化学将内在的H2O2转化为剧毒的活性氧来破坏癌细胞。除化学治疗作用外，顺铂还可以充当人工酶，通过级联反应为CDT产生H2O2，从而显着提高抗肿瘤效果。本文中，使用表没食子儿茶素-3-没食子酸酯（EGCG），酚类铂（IV）前药（Pt-OH）和多酚改性嵌段共聚物（PEG-b-PPOH）构建了具有高负载能力的有机治疗药物纳米药物（PTCG NPs）作为构建基块。 PTCG NP在循环过程中的高度稳定性源于它们与金属和多酚的强相互作用，并且在细胞内化后实现了有效的药物释放。激活的顺铂通过级联反应提高细胞内H2O2的水平。通过铁基Fenton反应，可将其进一步用于生产剧毒的活性氧。体外和体内研究表明，化学疗法和化学动力学疗法的组合可实现出色的抗癌功效。同时，通过这种纳米配方避免了铂类药物面临的全身毒性。这项工作为开发用于级联癌症治疗的先进纳米药物提供了有希望的策略。

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