Characteristics of DEAE-dextran-MMA graft copolymer as a nonviral gene carrier

摘要

A stable and soapless latex of diethylammoethyl-dextran-methyl methacrylate (DEAE-dextran-MMA) graft copolymer (DDMC) has been developed for nonviral gene delivery vectors that are possible to autoclave.DDMC relatively easily formed a polyion complex between DNA and DDMC by the hydrophobic force of graft poly(MMA) depending on its large positive entropy change (AS).DDMC has been confirmed as having a high protection facility for DNase by DNase degradation testTransfection activity was determined using the beta-galactosidase assay,and a higher value of 16 times or more was confirmed for the DDMC samples in comparison with one of the starting DEAE-dextran hydrochloride samples.The resulting DDMC,having an amphiphilic domain so as to form a polymer micelle,should become a stable latex with a hydrophilic-hydrophobic microseparated domain.The complex of DDMC and plasmid DNA may be formed on the spherical structure of the amphiphilic microseparated domain of DDMC and have a good affinity to the cell membrane.The infrared absorption spectrum shift to a high-energy direction at around 3450 cm~(-1),because of the complexes between DNA and DDMC,may cause the formation of more compact structures,not only by a coulomb force between the phosphoric acid of DNA and the DEAE group of DEAE-dextran copolymer but also by a force from the multi-intermolecule hydrogen bond in the backbone polymer DEAE-dextran and a hydrophobic force from the graft poly(MMA) in DDMC.It is thus concluded that DNA condensation may possibly have a high transfection efficiency via DDMC.The high efficiency of this graft copolymer,which is sterilized by an autoclave,may thus make it a valuable tool for safe gene delivery.