期刊
CARBOHYDRATE POLYMERS
卷 174, 期 -, 页码 1059-1068出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2017.07.035
关键词
RGD; Chitosan; PC3 cell; Tumor-xenograft; Polyethyleneimine
资金
- Basic Science Research Program through National Research Foundation of Korea (NRF) [NRF-2016R1D1A3A03918533, NRF-2017R1A2B4010831]
The safe and effective delivery of genetic material into cells is a necessary factor for gene therapy. Although a wide range of materials, methods, and combinations have been reported, successful genetherapy has been limited. In the present study, a targeted gene carrier for alpha(v)beta(3) integrin-overexpressing tumor cells was designed using widely applied materials containing water soluble chitosan (WSC), RGD peptide, and polyethyleneimine (PEI). The physiological characteristics, in vitro targeted gene transfection, cytotoxicity, blood-compatibility, and cellular distributions were investigated. In particular, astudy of the endocytic mechanism revealed processes of microtubule-dependent macropinocytosis andclathrin mediated endocytosis. Furthermore, the PEI/WSC copolymer with a dendrimer RGD peptide(four-branched RGD moiety) as a targeting moiety suppressed the growth of a solid tumor mass in vivo mouse xenograft model generated with PC3 prostate tumor cells by silencing BCL2 mRNA. This result indicated RGD/PEI/WSC copolymer for a good candidate as a simple and biocompatible gene carrier. (C) 2017 Elsevier Ltd. All rights reserved.
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