Bicomponent polymeric micelles for pH-controlled delivery of doxorubicin

Drug Delivery

Chunyun Wang¹  Lei Liu¹  Shiyong Song¹  Tianshun Wang¹  Mengying Zhang¹  Qianli Sheng¹  Yan Lu¹  Yanan Zhang¹  Rui Wang¹  Peilan Qi¹ 

[1] Institute of Pharmacy, School of Pharmacy, Henan University, Kaifeng, Chin;

关键词: Drug delivery;    pH-responsive;    micelle;    boronate ester;    cancer;   

DOI  :  10.1080/10717544.2020.1726526

来源: publisher

【 摘 要 】

Stimuli-responsive drug delivery systems (DDSs) are expected to realize site-specific drug release and kill cancer cells selectively. In this study, a pH-responsive micelle was designed utilizing the pH-sensitivity of borate bonds formed between dopamine and boronic acid. First, methyl (polyethylene glycol)-block-polycaprolactone (mPEG-PCL) was conjugated with 4-cyano-4-(thiobenzoylthio)pentanoic acid (CTP) to obtain a macroinitiator. Two different segments poly(dopamine methacrylamide) (PDMA) and poly(vinylphenylboronic acid) (PVBA) were then grafted to the end of mPEG-PCL. Two triblock copolymers, mPEG-PCL-PDMA and mPEG-PCL-PVBA, were then obtained by reversible addition–fragmentation transfer (RAFT) polymerization. These copolymers and their mixture self-assembled in aqueous solution to form micelles that were able to load hydrophobic anticancer drug doxorubicin (DOX). These two-component micelles were found to be pH-sensitive, in contrast to the one-component micelles. Furthermore, MTT studies showed that the micelles were almost nontoxic. The DOX-loaded micelles showed cytotoxicity equivalent to that of DOX at high concentration. In vivo antitumor experiments showed that this pH-sensitive polymeric micellar system had an enhanced therapeutic effect on tumors. These two-component boronate-based pH micelles are universally applicable to the delivery of anticancer drugs, showing great potential for cancer therapy.

【 授权许可】

CC BY