Redox-sensitive micelles based on retinoic acid modified chitosan conjugate for intracellular drug delivery and smart drug release in cancer therapy

被引:38
|
作者
Luo, Tingting [1 ]
Han, Jingtian [1 ]
Zhao, Feng [1 ]
Pan, Xiaohong [1 ]
Tian, Baocheng [1 ]
Ding, Xiujuan [1 ]
Zhang, Jing [1 ]
机构
[1] Binzhou Med Univ, Sch Pharm, 346 Guanhai Rd, Yantai 264003, Peoples R China
基金
中国国家自然科学基金;
关键词
Paclitaxel; Redox-sensitive; Retinoic acid; Polymeric micelles; Chitosan; LOW-DENSITY-LIPOPROTEIN; CO-DELIVERY; MIXED MICELLES; POLYMERIC NANOPARTICLES; TARGETED DELIVERY; TUMOR-CELLS; IN-VITRO; PACLITAXEL; REDUCTION; PH;
D O I
10.1016/j.carbpol.2019.03.064
中图分类号
O69 [应用化学];
学科分类号
081704 ;
摘要
Novel chitosan-cystamine-retinoic acid conjugate (CS-SS-RA) was synthesized and could self-assemble into redox-sensitive micelles in aqueous environment with low critical micelle concentration value. CS-SS-RA micelles were characterized with spherical shape, desirable particle size, negative zeta potential, high paclitaxel (PTX) loading and encapsulation efficiency and redox-sensitivity. Hemolysis and cytotoxicity studies proved the safety of CS-SS-RA micelles for intravenous administration. Cytotoxicity study against HepG2 cells and the growth inhibition study on three-dimensional multicellular tumor spheroids (MCTSs) revealed that PTX-loaded CS-SS-RA micelles exhibited higher antitumor activity than free PTX. The in vitro cellular uptake profiles of FITC-labeled CS-SS-RA micelles evaluated via confocal laser scanning microscopy and flow cytometry indicated that CS-SS-RA micelles could enhance cellular uptake efficiency of PTX, and their internalization by HepG2 cells were mediated by clathrin-mediated endocytosis and macropinocytosis. These results demonstrated that CS-SS-RA micelles could be developed as a promising platform for intracellular delivery of hydrophobic antitumor agents.
引用
收藏
页码:8 / 19
页数:12
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