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J Biomater Sci Polym Ed. 2012;23(5):677-95. doi: 10.1163/092050611X558297. Epub 2011 Mar 4.

Study on galactose-poly(ethylene glycol)-poly(L-lysine) as novel gene vector for targeting hepatocytes in vitro.

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  • 1Guang Dong Pharmaceutical University, Guangzhou 510006, P. R. China. gzhm368@163.com

Abstract

A non-viral gene-delivery system has been used to deliver plasmid DNA into specific cell types because of its safety and ease of manufacture. Receptor-mediated gene transfer is currently a promising gene-delivery technique. To specifically target genes to asialoglycoprotein receptor of hepatocytes, a galactose moiety was combined into the poly(ethylene glycol) (PEG)-terminal end by reductive coupling using lactose and sodium cyanoborohydride. A synthesis method of conjugating poly(L-lysine) (PLL) derivatives with terminally galactose-graft-PEG was developed using ring-opening polymerization of N(ε)-benzyloxycarbonyl-L-lysine-N(α)-carboxyan-hydride (Z-Lys-NCA) initiated onto galactose graft amine-terminated PEG (galactose-PEG-NH₂) as a macro-initiator. The synthesis was characterized with ¹H-, ¹³C-NMR, IR and UV spectroscopy, and all of them successfully verified the formation of the co-polymers. The gel-retardation assay of the complexes between galactose-PEG-PLL and plasmid DNA indicated that these polymeric gene carriers demonstrated the potent ability to condense plasmid DNA electrostatically as well as PLL. The particle size and zeta potential of polymer/DNA complexes were measured, and their cytotoxicity and transfection efficiency in different cells were evaluated. The results indicate that galactose-PEG-PLL can form a complex with plasmid DNA and serve as an effective gene-delivery carrier with lower cytotoxicity compared to that of PLL. Transfection experiments clearly showed that galactose-PEG-PLL effectively delivered DNA into hepatoma cells in vitro. Such data demonstrates that galactose and its complex with plasmid DNA may serve as a safe and effective gene-transfer system targeting hepatocytes.

PMID:
21375808
DOI:
10.1163/092050611X558297
[PubMed - indexed for MEDLINE]
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