期刊
BIOMATERIALS
卷 58, 期 -, 页码 35-45出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2015.04.034
关键词
Programmed packaging; PEG deshielding; Matrix metalloproteinases 2; Gelatin; Tumor targeting
资金
- National Natural Science Foundation of China [21175039, 21322509, 21305035, 21305038, 21190044, 21221003]
- Key Technologies Re-search and Development Program of China [2011AA02a114]
- Research Fund for the Doctoral Program of Higher Education of China [20110161110016]
- Hunan Provincial Natural Science Foundation [14JJ3066]
- Hunan Provincial Innovation Foundation for Postgraduate [CX2013B138]
The development of multifunctional nanocarrier with each unit functioning at the correct time and location is a challenge for clinical applications. With this in mind, a type of intelligent mesoporous silica nanocarrier (PGFMSN) is proposed for matrix metalloprotease 2 (MMP 2)-triggered tumor targeting and release by integrating programmed packing and MMP 2-degradable gelatin. Mesoporous silica nanoparticles (MSN) are first functionalized with folic acid (FA) as a target ligand to improve cell uptake. Then gelatin is introduced onto FA-MSN via temperature-induced gelation, where gelatin layer blocks drugs inside the mesopores and protects the targeting ligand. To prolong blood-circulation lifetime, PEG is further decorated to obtain PGFMSN. All units are programmatically incorporated in a simple way and coordinated in an optimal fashion. Cells, multicellular spheroids and in vivo results demonstrate that PGFMSN is shielded against nonspecific uptake. After circulating to tumor tissue, the up-regulated MMP-2 hydrolyzes gelatin layer to deshield PEG and switch on the function of FA, which facilitate the selective uptake by tumor cells through folate-receptor-mediated endocytosis. Meanwhile, the packaged drug is released due to the shedding of gelatin layer. It is shown that doxorubicin (DOX)-loaded exhibits superior tumor targeting, drug internalization, cytotoxicity, and antitumor efficacy over free DOX, non-PEGylated and non-targeted nanoparticles, which provides potential applications for targeted cancer therapy. (C) 2015 Elsevier Ltd. All rights reserved.
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