Tumor microenvironment-responsive docetaxel-loaded micelle combats metastatic breast cancer
Tumor microenvironment-responsive docetaxel-loaded micelle combats metastatic breast cancer
复制标题
肿瘤微环境响应的多西他赛负载胶束对抗转移性乳腺癌
DOI：
10.1016/j.scib.2018.12.025
复制
发表时间：
2019-01-30
期刊：
影响因子：
18.9
通讯作者：
Li, Yaping
中科院分区：
文献类型：
--
作者：
Lang, Tianqun;Dong, Xinyue;Li, Yaping
Efficient tumor-targeting drug delivery systems are urgently needed for treating metastatic breast cancer. In this work, a docetaxel (DTX)-loaded micelle (pDM) as the tumor-microenvironment-responsive delivery platform is developed. The micelle is composed of a pH-sensitive amphiphilic copolymer, poly((1,4-butanediol)-diacrylate-beta-N, N-diisopropylethylenediamine)-polyethyleneimine (BD-PEI), and a matrix metalloproteinase (MMP)-responsive polymer, poly((1,4-butanediol)-diacrylate-beta-N, N-diisopropy lethylenediamine)-peptide-polyethylene glycol (PEG) (BD-peptide-PEG). The PEG block of BD-peptide-PEG will be split by MMPs at the tumor microenvironment, which leads to the change of the surface charge and particle size of the micelle to more positive and smaller one. Owing to this transformation and enhanced permeability and retention (EPR) effect, pDM delivers more DTX into tumor tissues and is internalized more efficiently by tumor cells than the non-MMP-sensitive micelles in the 4T1 tumor-bearing mice model. In addition, DTX is released in acidic endo/lysosomes due to the dissociation of the micelle, triggered by the protonation of the hydrophobic block of BD-PEI. As a result, the DTX-loaded micelle inhibits primary tumor growth and pulmonary metastasis effectively. Thus, this pH/MMP-dual-sensitive drug delivery system, which simultaneously attains three keypoints: prolonged circulation time, directional and efficient uptake into tumor cells, and speedy intracellular drug release, is a promising strategy for metastatic breast cancer therapy. (C) 2018 Science China Press. Published by Elsevier B.V. and Science China Press. All rights reserved.
