A self-targeting and controllable drug delivery system constituting mesoporous silica nanoparticles fabricated with a multi-stimuli responsive chitosan-based thin film layer

被引:69
作者
Chen, Chao [1 ]
Yao, Wenji [1 ]
Sun, Wen [1 ]
Guo, Tianyuan [1 ]
Lv, Hangya [1 ]
Wang, Xiaoli [1 ]
Ying, Hanjie [1 ,2 ]
Wang, Yibing [1 ]
Wang, Ping [1 ]
机构
[1] East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai Collaborat Innovat Ctr Biomfg Technol, Biomed Nanotechnol Ctr,Sch Biotechnol, 130 Meilong Rd, Shanghai 200237, Peoples R China
[2] Nanjing Tech Univ, Coll Biotechnol & Pharmaceut Engn, State Key Lab Mat Oriented Chem Engn, 30 Puzhu South Rd, Nanjing 211816, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Mesoporous silica nanoparticles; pH/GSH dual-responsive; Target drug delivery; CONTROLLED-RELEASE; FOLIC-ACID; PH; NETWORK; CELLS;
D O I
10.1016/j.ijbiomac.2018.09.058
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Surface modification and functionalization of nanomaterials have been adopted widely in devising smart drug delivery systems. This work examines the fabrication of multi-stimuli responsive surfaces on mesoporous silica nanoparticles (MSN) for environmentally sensitive site specific drug delivery with reduced risk of premature drug leakage. Chitosan cross-linked via disulfide bonds was applied to form a thin film on drug-loaded MSN, realizing a capsulation and stimuli-sensitive regulating gate membrane; that was further conjugated with folate for site specific targeting toward cancer cells. The chitosan thin film was very stable under neutral conditions and could effectively prevent drug leakage, but was sensitive to both pH and GSH stimulations to reach rapid drug release. Thus, drug release could be triggered by changes in such factors that are common to cancer cells. However, complete and accelerated release could only be realized when triggered simultaneously by both acidic pH and GSH. Moreover, tests with HepG-2 cells confirmed that folate-receptor mediated endocytosis successfully enhanced the cellular uptake of the nanoparticle and antitumor activity toward cancer cells. It is expected that this surface chemical modification strategy promises a powerful approach constructing smart drug delivery systems for efficient and safe chemotherapy. (C) 2018 Elsevier B.V. All rights reserved.
引用
收藏
页码:1090 / 1099
页数:10
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