文献类型：期刊文献

英文题名：Cancer-targeted and glutathione-responsive micellar carriers for controlled delivery of cabazitaxel

作者：Han, Xiaoxiong[1];Gong, Feirong[2];Chi, Lili[3];Feng, Caochuan[1];Sun, Jing[1];Chen, Yiyang[4];Liu, Jianwen[4];Shen, Yaling[1]

机构：[1]East China Univ Sci & Technol, Shanghai Collaborat Innovat Ctr Biomfg Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Mat Sci & Engn, Key Lab Ultrafine Mat, Minist Educ, Shanghai 200237, Peoples R China;[3]Shandong Univ Tradit Chinese Med, Dept Gastroenterol, Affiliated Hosp, Jinan 250011, Shandong, Peoples R China;[4]East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China

年份：2019

卷号：30

期号：5

外文期刊名：NANOTECHNOLOGY

收录：;EI(收录号：20185106265992);WOS:【SCI-EXPANDED(收录号:WOS:000452423000001)】；

基金：This work was supported by the National Special Fund for State Key Laboratory of Bioreactor Engineering (No. 2060204); and the National Natural Science Foundation of China (No. 81673969).

语种：英文

外文关键词：GSH-responsive; tumor-targeting peptide; cabazitaxel; polymeric micelles

摘要：Novel type of multifunctional polymeric micelles (PMs) designated as HM-PMss/CTX micelles were developed in the present study for tumor-targeted and glutathione (GSH)-responsive delivery of cabazitaxel (CTX). The surface of the vehicles was modified with piloting molecules (HM-3 peptide), which targets alpha(v)beta(3) integrin overexpressed on cancer cells, and the micelle core was cross-linked by GSH-disintegrable disulfide linkages for controlled drug release. HM-PMss/CTX micelles were prepared using a mixture of two functionalized amphiphilic block copolymers and found to physically encapsulate CTX with excellent entrapment efficiency (93.94 +/- 4.19%), drug-loading capacity (8.39 +/- 2.28%), and a narrow size distribution. In vitro release profiles showed that CTX remained stably entrapped in the micelles in a release medium without GSH or with GSH of low concentration, while undergoing a rapid release in a highly reductive environment. Cellular uptake experiments showed that the conjugation of the targeting peptide, containing an arginine-glycine-aspartate sequence, enhanced the cellular uptake of HM-PMss/CTX micelles via alpha(v)beta(3) integrin-mediated endocytosis. In vitro cell viability measurements revealed that blank micelles were biocompatible, while HM-PMss/CTX micelles, owing to their tumor-targeting ability and GSH sensitivity, effectively inhibited the proliferation of MDA-MB-231 breast cancer cells. These results indicate that HM-PMss/CTX micelles could be a promising platform for future intelligent drug delivery in cancer therapy.