Colloids and Surfaces B: Biointerfaces 2014-07-01

Endosomal pH responsive polymers for efficient cancer targeted gene therapy.

Bingyang Shi, Hu Zhang, Jingxiu Bi, Sheng Dai

Index: Colloids Surf. B Biointerfaces 119 , 55-65, (2014)

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Abstract

Treatment of human diseases at gene level is always limited by effective gene delivery vectors. In this study, we designed and developed an endosomal pH sensitive targeted gene delivery system, folic acid functionalized Schiff-base linked imidazole chitosan (FA-SLICS), for cancer therapy. The FA-SLICS is able to self-assemble plasmid DNA (pDNA) into nano-scaled polyplexes under a neutral condition and to release the loaded pDNA in the endosomal microenvironment due to the presence of pH sensitive Schiff-base moieties along chitosan backbones. The FA-SLICS has negligible cytotoxicity to normal cells (CHO), but displays slight toxicity to cancer cells (HeLa and HepG2). In addition, FA-SLICS can selectively and efficiently transfect FR (folate receptor) positive cells (HeLa cells) as a gene carrier. Therefore, the FA-SLICS should be a promising delivery vector in cancer gene therapy based on its cell targeting capability and intracellular microenvironment controlled delivery mechanism. Copyright © 2014 Elsevier B.V. All rights reserved.