胶束
肿瘤微环境
多西紫杉醇
化学
癌症研究
聚乙二醇
药物输送
生物物理学
癌症
医学
生物化学
内科学
有机化学
肿瘤细胞
生物
水溶液
作者
Tianqun Lang,Xinyue Dong,Zhong Zheng,Yiran Liu,Guanru Wang,Qi Yin,Yaping Li
标识
DOI:10.1016/j.scib.2018.12.025
摘要
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-β-N,N-diisopropylethylenediamine)-polyethyleneimine (BD-PEI), and a matrix metalloproteinase (MMP)-responsive polymer, poly((1,4-butanediol)-diacrylate-β-N,N-diisopropylethylenediamine)-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.
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