Bicomponent polymeric micelles for pH-controlled delivery of doxorubicin. (1st January 2020)

• Record Type: Journal Article
• Authors: Wang, Chunyun; Qi, Peilan; Lu, Yan; Liu, Lei; Zhang, Yanan; Sheng, Qianli; Wang, Tianshun; Zhang, Mengying; Wang, Rui; Song, Shiyong
• Is Part Of: Drug delivery. Volume 27:Number 1(2020)
• Page Start: 344
• Page End: 357
• Publication Date: 2020-01-01
• Subjects: Drug delivery -- pH-responsive -- micelle -- boronate ester -- cancer; Drug delivery systems -- Periodicals; Drug targeting -- Periodicals; 615.05
• DOI: 10.1080/10717544.2020.1726526
• Languages: English
• ISSNs: 1071-7544

Abstract

Abstract: 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.