Preparation of dendritic graft copolymer consisting of poly(L-lysine) and arabinogalactan as a hepatocyte specific dna carrier

The dendriTIc graft copolymers (PAX) consisting of a poly(L-lysine) (PLL) m ain chain and grafts of arabinogalactan (AG) were prepared as a liver cell- specific DNA carrier. The copolymers were successfully prepared by reductiv e amination reaction between a reductive end of AG and E-amino groups of PL L using NaBH3CN as a catalyst. The fractionation of a low molecular weight fraction (Mn = 25 kDa) from a crude AG (Mn = 33 kDa) was essential for the reaction to proceed. The resulting copolymers were isolated ultrafiltration from unreacted AG and characterized by H-1 NMR and gel permeation chromato graphy equipped with a multiangle laser light scattering detector (GPC-MALL S). The binding and internalization of DNA to hepatoma cells, HepG2, were consi derably enhanced by complexing DNA with PAX copolymers. The interactions be tween PAX/DNA complexes and HepG2 cells were thoroughly inhibited in the pr esence of a competitor to asialoglycoprotein receptors (ASGP-R), indicating high specificity of the complex to ASGP-R. Furthermore, the PAX copolymers allowed the expression of the reporter gene. Our results reveal that the P AX copolymers may provide a new research tool for cell-specific gene delive ry and eventually enhance gene-therapy technology.