Hypochlorous Acid Promoted Platinum Drug Chemotherapy by Myeloperoxidase-Encapsulated Therapeutic Metal Phenolic Nanoparticles
Hypochlorous Acid Promoted Platinum Drug Chemotherapy by Myeloperoxidase-Encapsulated Therapeutic Metal Phenolic Nanoparticles
复制标题
次氯酸促进髓过氧化物酶封装的治疗性金属酚醛纳米颗粒的铂类药物化疗
DOI：
10.1021/acsnano.7b06852
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发表时间：
2018-01-01
期刊：
影响因子：
17.1
通讯作者：
Chen, Xiaoyuan
中科院分区：
文献类型：
--
作者：
Dai, Yunlu;Cheng, Siyuan;Chen, Xiaoyuan
本研究应用原位生成次氯酸（HOCl）来提高铂类药物的疗效。髓过氧化物酶（MPO）是由两种功能性多酚衍生物（铂前体多酚和PEG多酚）和铁离子通过金属酚配位作用包覆在吞噬酶上，从而保护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（11202）。MPO催化11202在细胞间环境中转化为HOCl。所制备的MPO Pt PEG纳米颗粒（MPP NPs）可用作活性氧级联生物反应以增强铂药物治疗。MPP NP显示延长的血液循环和高肿瘤积聚，如通过基于Zr-89的正电子发射断层扫描成像所证明的。MPP NP在体内有效地抑制肿瘤生长。作为利用纳米医学中的高毒性HOCl进行癌症治疗的一流平台，这种策略可能为进一步开发渐进式治疗系统打开大门。
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 (11202). The MPO catalyzes the conversion of 11202 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 Zr-89-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.