Bioresponsive Controlled Drug Release Based on Mesoporous Silica Nanoparticles Coated with Reductively Sheddable Polymer Shell

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• 作者：Baisong Chang ; Dan Chen ; Yang Wang ; Yanzuo Chen ; Yunfeng Jiao ; Xianyi Sha ; Wuli Yang
• 刊名：Chemistry of Materials
• 出版年：2013
• 出版时间：February 26, 2013
• 年：2013
• 卷：25
• 期：4
• 页码：574-585
• 全文大小：603K
• 年卷期：v.25,no.4(February 26, 2013)
• ISSN：1520-5002

文摘

The design of bioresponsive controlled drug delivery systems is a promising approach in cancer therapy, but it still is a major challenge capable of optimum therapeutic efficacy, i.e. no premature drug leakage in blood circulation while having a rapid and complete release in tumor tissues. In this work, a kind of PEGylated core/shell structured composite nanoparticle was developed via precipitation polymerization, where a disulfide-cross-linked poly(N-vinylcaprolactam-co-methacrylic acid) (P(VCL-s-s-MAA)) polymer shell was created to act as sheddable thermo/pH-sensitive gatekeepers, and a carboxylic acid modified mesoporous silica nanoparticles (MSN-COOH) core was applicable as an accessible reservoir to encapsulate high drug doses. At physiological conditions, the P(VCL-s-s-MAA)-PEG shell underwent a distinct transition from a swollen state in pH 7.4 to a collapsed state in pH 5.0. Though sufficiently stable in water, composite nanoparticles were prone to fast dissociation and rupture when subjecting to 10 mM glutathione (GSH), due to the shedding of polymer walls through reductive cleavage of intermediate disulfide bonds, so that the polymer shell was active in moderating the diffusion of embedded drugs in-and-out of MSN channels. The cumulative in vitro release of DOX-loaded composite nanoparticles allowed a low trace of DOX diffusion below volume phase transition temperature (VPTT) and a significant release rate above its VPTT, while the most rapid and perfect release was achieved under a reductive environment (pH 6.5 and 10 mM GSH), mimicking that of intracellular cytosol compartments. The in vitro cell assay of blank carriers to normal cells indicated that the composite nanoparticles were suitable as drug carriers, but DOX-loaded carriers had a similar intensive toxicity to cancer cells compared with free DOX. Therefore, these stimuli-responsive composite nanoparticles with a reductively sheddable and thermo/pH-responsive polymer shell gate could, in principle, be applied for in vivo cancer therapy, and synergistic drug delivery can be accomplished 鈥渏ust in time鈥?in a precise event over the location.

Keywords:

thermo/pH-responsive; shell-sheddable; core/shell; MSN; controlled drug release