Targeted gene delivery of polyethyleneimine-grafted chitosan with RGD dendrimer peptide in αvβ3 integrin-overexpressing tumor cells

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.