Dextran-spermine polycation: an efficient nonviral vector for in vitro and in vivo gene transfection.
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.
Hosseinkhani
H
H
Department of Biomaterials, Field of Tissue Engineering, Kyoto University, Kyoto, Japan.
Azzam
T
T
Tabata
Y
Y
Domb
A J
AJ
D016475:3T3 Cells; D000818:Animals; D002412:Cations; D002460:Cell Line; D004247:DNA / Q000008:administration & dosage*; D003911:Dextrans / Q000235:genetics*; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics*; D006801:Humans; D007273:Injections, Intramuscular; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D011092:Polyethylene Glycols; D013096:Spermine / Q000378:metabolism*; D014162:Transfection / Q000379:methods*; D001616:beta-Galactosidase / Q000235:genetics
D002412:Cations; D003911:Dextrans; D013096:Spermine; D011092:Polyethylene Glycols; D004247:DNA; D001616:beta-Galactosidase