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

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. In this study, we report a unique pH/GSH dual responsive smart drug delivery system that can effectively prevent premature leakage of drug load. Toward that, chitosan molecules cross-linked via disulfide bonds were 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. [Display omitted] •A novel type of FA-receptor targeted and pH/GSH dual-responsive smart drug delivery system was prepared and characterized.•Chitosan cross-linked via disulfide bonds was applied to form a thin film covered on the surface of MSN.•The chitosan thin film was very stable under neutral conditions and could sensitive to both pH and GSH stimulations.•The obtained targeted nanohybrids showed significantly higher cytotoxicity to HepG-2 cells than to L-02 cells.