文献类型：期刊文献

英文题名：Synthesis, characterization, and in vitro evaluation of TRAIL-modified, cabazitaxel -loaded polymeric micelles for achieving synergistic anticancer therapy

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

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

年份：2018

卷号：29

期号：14

起止页码：1729

外文期刊名：JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION

收录：;EI(收录号：20182405313988);WOS:【SCI-EXPANDED(收录号:WOS:000448728400006)】；

语种：英文

外文关键词：Cabazitaxel; TRAIL; polymeric micelles; synergism; anticancer

摘要：Combination therapy of two or more drugs has gradually become of outmost importance in cancer treatment. Cabazitaxel (CTX) is a taxoid drug and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of TNF superfamily. In this study, we prepared TRAIL-modified and CTX-loaded polymer micelle (TRAIL-M-CTX). This nanoparticle was self-assembled from biodegradable amphiphilic copolymers, monomethoxyl poly(ethylene glycol)-b-poly(DL-lactide) (mPEG-PLA) and COOH-PEG-PLA, via a nanoprecipitation method and were modified with the TRAIL protein, resulting in a particle size of 39.75 +/- 0.17nm in diameter and a drug encapsulation efficiency of 95.52 +/- 1.69%. The successful coupling was confirmed by H-1 NMR, FTIR spectroscopy, and DLS article size measurement. Pharmacodynamic analysis in two human cancer cell lines with different TRAIL sensitivities showed that TRAIL-M-CTX has a significantly better anticancer efficacy than the individual CTX and TRAIL protein. Importantly, TRAIL-M-CTX showed synergistic effects against TRAIL-insensitive cells (MCF-7). A study of cellular uptake implied that the modified micelles were internalized into MCF-7 cells more effectively than unmodified micelles, owing to the coupled TRAIL protein. A cell cycle assay of MCF-7 cells revealed that TRAIL-M-CTX significantly increased the sub-G1 population compared with CTX or TRIAL, thus, facilitating cancer cell apoptosis. These results suggest that TRAIL-M-CTX micelles have potential as a cancer chemotherapy formulation.