Sun Changzhen, Liang Yan, Hao Na, Xu Long, Cheng Furong, Su Ting, Cao Jun, Gao Wenxia, Pu Yuji, He Bin
National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China.
Org Biomol Chem. 2017 Nov 7;15(43):9176-9185. doi: 10.1039/c7ob01975k.
As the implications of reactive oxygen species (ROS) are elucidated in many diseases, ROS-responsive nanoparticles are attracting great interest from researchers. In this work, a ROS sensitive thioketal (TK) moiety with a π-conjugated structure was introduced into biodegradable methoxy poly(ethylene glycol)-thioketal-poly(ε-caprolactone)mPEG-TK-PCL micelles as a linker, which was designed to speed up the drug release and thus enhance the therapeutic efficacy. The micelle showed a high drug loading content of 12.8% and excellent stability under physiological conditions because of the evocation of π-π stacking and hydrophobic interactions with the anticancer drug doxorubicin (DOX). The polymeric micelle presented a better drug carrier capacity and higher in vitro anticancer efficacy towards cancer cells. The in vivo study showed that DOX-loaded mPEG-TK-PCL micelles displayed lower toxicity towards normal cells and remarkably enhanced antitumor efficacy. This research provides a way to design potential drug carriers for efficient cancer chemotherapy.
随着活性氧（ROS）在许多疾病中的作用被阐明，ROS响应性纳米颗粒正吸引着研究人员的极大兴趣。在这项工作中，一种具有π共轭结构的ROS敏感硫酮（TK）部分被引入到可生物降解的甲氧基聚（乙二醇）-硫酮-聚（ε-己内酯）（mPEG-TK-PCL）胶束中作为连接体，其设计目的是加速药物释放从而提高治疗效果。由于与抗癌药物阿霉素（DOX）发生π-π堆积和疏水相互作用，该胶束显示出12.8%的高载药量以及在生理条件下的优异稳定性。该聚合物胶束表现出更好的药物载体能力以及对癌细胞更高的体外抗癌效果。体内研究表明，载有DOX的mPEG-TK-PCL胶束对正常细胞显示出较低毒性，并显著增强了抗肿瘤效果。这项研究为设计用于高效癌症化疗的潜在药物载体提供了一种方法。
