"Stealthy" chitosan/mesoporous silica nanoparticle based complex system for tumor-triggered intracellular drug release

被引：36

作者：

Zhang M. ^{[1
]}

Liu J. ^{[2
]}

Kuang Y. ^{[3
]}

Li Q. ^{[2
]}

Chen H. ^{[1
]}

Ye H. ^{[1
]}

Guo L. ^{[1
]}

Xu Y. ^{[4
]}

Chen X. ^{[1
]}

Li C. ^{[1
]}

Jiang B. ^{[1
]}

机构：

[1] Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Key Laboratory for the Green Preparation and Application of Functional Materials, Ministry of Education, Hubei University, Wuhan, Hubei

[2] Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei

[3] Department of Food Science and Technology, School of Bio-engineering, Hubei University of Technology, Wuhan, Hubei

[4] Hubei Research Institute of Products Quality Supervision and Inspection, Wuhan, Hubei

来源：

Journal of Materials Chemistry B | 2016年 / 4卷 / 19期

基金：

中国国家自然科学基金;

关键词：

Controlled drug delivery - Diseases - Polyethylene oxides - Targeted drug delivery - Cancer cells - Tumors - Covalent bonds - Silica nanoparticles - Sulfur compounds - Histology - Cells - Polyethylene glycols;

D O I：

10.1039/c5tb02548f

中图分类号：

学科分类号：

摘要：

Suitable protection strategies utilized in anticancer drug delivery systems enable carriers to reach their targeted positions and release drugs intracellularly more effectively. In this study, a novel "stealthy" chitosan (CHI)/mesoporous silica nanoparticle (MSN) based complex system, named DOX@MSN-SS-CHI-PEG, was developed for tumor-triggered intracellular drug release. CHI was applied to block the pores of MSNs to prevent premature drug release, whereas mPEG was grafted on the surface of the nanoparticles via a pH-sensitive benzoic imine linker to protect the carriers. As the pH of solid tumor tissues is slightly lower than that of normal tissues, mPEG could leave the nanoparticles to expose positively charged CHI at the surface, which enabled the nanoparticles to enter cancer cells more easily. The MSNs were covered by CHI via redox-sensitive disulfide bonds. As a result, the carriers could release the drug intercellularly to kill cancer cells owing to the high concentration of glutathione (GSH) in the cytosol. In vitro drug release studies at different GSH concentrations proved the redox-sensitivity of DOX@MSN-SS-CHI-PEG. mPEG leaving studies demonstrated that mPEG could leave the nanoparticles effectively at pH 6.0. The cytotoxicity and cell internalization behavior were also investigated in detail. In conclusion, the novel DOX@MSN-SS-CHI-PEG drug delivery system, which was "stealthy" in the physiological environment at pH 7.4 because of the protection of mPEG, was "activated" in weakly acidic tumor tissues to achieve tumor-triggered intracellular drug release; this system has great potential for cancer therapy. © 2016 The Royal Society of Chemistry.

引用

页码：3387 / 3397

页数：10

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