Journal
GENE THERAPY
Volume 20, Issue 6, Pages 597-606Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/gt.2012.72
Keywords
tumor gene therapy; gene delivery; chitosan oligosaccharide; polyethylenimine; polymeric micelles; plasmid pigment epithelium derived factor
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Funding
- National Nature Science Foundation of China [30873174, 81072583]
- Nature Science Foundation of Zhejiang province [z207489, Y2090336]
- Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents
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Non-viral vesicle composing of low-molecular weight polyethylenimine-conjugated stearic acid-g-chitosan oligosaccharide (CSOSA-g-PEI) was synthesized for gene delivery and therapy. The synthesized CSOSA-g-PEI had good ion-buffer capabilities and DNA-binding capacity, which could form positively charged nano-sized particles (100-150 nm) with plasmid DNA; in vitro gene transfection tests demonstrated that CSOSA-g-PEI presented much lower cytotoxicity and corresponding transfection efficiency in comparison with Lipofectamine 2000 in both human cancer cells (Hela and MCF-7). The gene transfection of CSOSA-g-PEI/pDNA could be further enhanced in the presence of serum or by adding arginine during incubation of CSOSA-g-PEI micelles with plasmid DNA. The biodistribution experiments demonstrated CSOSA-g-PEI conjugate highly localized in the tumor tissue and indicated a persistently increased accumulation. In vivo antitumor activity results showed that CSOSA-g-PEI/plasmid pigment epithelium-derived factor formulation could effectively suppress the tumor growth (above 60% tumor inhibition) without systematic toxicity against animal body after intravenous injection.
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