Hypochlorous Acid Promoted Platinum Drug Chemotherapy by Myeloperoxidase-Encapsulated Therapeutic Metal Phenolic Nanoparticles

被引：150

作者：

Dai, Yunlu ^{[1
,2
]}

Cheng, Siyuan ^{[2
]}

Wang, Zhongliang ^{[1
]}

Zhang, Ruili ^{[1
]}

Yang, Zhen ^{[2
]}

Wang, Jingjing ^{[2
]}

Yung, Bryant C. ^{[2
]}

Wang, Zhantong ^{[2
]}

Jacobson, Orit ^{[2
]}

Xu, Can ^{[2
]}

Ni, Qanqian ^{[2
]}

Yu, Guocan ^{[2
]}

Zhou, Zijian ^{[2
]}

Chen, Xiaoyuan ^{[2
]}

机构：

[1] Xidian Univ, Sch Life Sci & Technol, Minist Educ, Engn Res Ctr Mol Imaging & Neuroimaging, Xian 710126, Shaanxi, Peoples R China

[2] NIH, Lab Mol Imaging & Nanomed LOMIN, NIBIB, Bethesda, MD 20892 USA

来源：

ACS NANO | 2018年 / 12卷 / 01期

基金：

中国国家自然科学基金; 美国国家卫生研究院;

关键词：

myeloperoxidase (MPO); metal-polyphenol networks; hypochlorous acid (HOCl); cisplatin; positron emission tomography; CANCER-THERAPY; PHOTODYNAMIC THERAPY; ACHILLES-HEEL; GENERATION; APOPTOSIS; CELLS; ROS; IMMUNOTHERAPY; MECHANISMS; NETWORKS;

D O I：

10.1021/acsnano.7b06852

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页码：455 / 463

页数：9

共 36 条

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