超分子化学
多酚
化学
硼替佐米
组合化学
纳米医学
纳米技术
药物输送
有机化学
抗氧化剂
分子
材料科学
纳米颗粒
生物
免疫学
多发性骨髓瘤
作者
Changping Wang,Huajun Sang,Yitong Wang,Fang Zhu,Xingyu Hu,Xinyu Wang,Yiwen Li,Yiyun Cheng
出处
期刊:Nano Letters
[American Chemical Society]
日期:2018-09-28
卷期号:18 (11): 7045-7051
被引量:103
标识
DOI:10.1021/acs.nanolett.8b03015
摘要
Bortezomib (BTZ) is a first-in-class boronate proteasome inhibitor used for cancer therapy, but its therapeutic efficacy is usually inhibited by dietary polyphenols due to boronate-catechol complexation. Benefiting from such dynamic covalent chemistry, herein we describe a novel class of supramolecular nanomedicines by rationally converting natural polyphenols from foe to friend through polyphenol-mediated BTZ assembly strategy. The simple conjugation of BTZ to catechol-containing natural polyphenols via boronate ester bond allows the facile formation of dynamic drug amphiphiles, with pH-dependent assembly/disassembly behaviors under different physiological conditions. Ferric ion was also incorporated into the supramolecular system via metal-phenolic coordination interaction to both introduce bioimaging function and facilitate stability of the supramolecular nanomedicines. Our investigation revealed that the supramolecular nanomedicine consisting of natural polyphenol, BTZ and ferric ion dramatically induced apoptosis on cancer cells and suppressed tumor growth in both subcutaneous and bone tumor models with limited adverse effects. Such natural polyphenol-mediated small drug assembly strategy enables the robust fabrication of supramolecular nanomedicines for efficient delivery and controlled release of BTZ in targeted tumor sites, which could be further employed in other types of boronic acid-containing supramolecular therapeutics toward a wide range of diseases.
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