Dextran-spermine polycation: An efficient nonviral vector for in vitro and in vivo gene transfection

Abstract

Dextran-spermine cationic polysaccharide was prepared by means of reductive amination between oxidized dextran and the natural oligoamine spermine. The formed Schiff-base imine-based conjugate was reduced with borohydride to obtain the stable amine-based conjugate. The transfection efficiency of the synthetic dextran-spermine was assessed in vitro on HEK293 and NIH3T3 cell lines and found to be as high as the DOTAP/Chol 1/1 lipid-based transfection reagent. Modification of the dextran-spermine polycation with polyethylene glycol resulted in high transfection yield in serum-rich medium. Intramuscular injection in mice of dextran-spermine-pSV-LacZ complex induced high local gene expression compared to low expression of the naked DNA. Intravenous injection of a dispersion of the dextran-spermine-pSV-LacZ complex resulted with no expression in all examined organs. When the partially PEGylated dextran-spermine-pSV-LacZ complex was intravenously applied, a high gene expression was detected mainly in the liver. Preliminary targeting studies indicated that the PEGylated dextran-spermine-pSV-LacZ complex bound to galactose receptor of liver parenchymal cells rather than the mannose receptor of liver nonparenchymal cells. This work offers a new biodegradable polycation based on natural components, which is capable of transfecting cells and tissues in vitro and in vivo.