DEAE-Dextran and DEAE-Dextran-MMA Graft Copolymer for Nanomedicine
Authors: YasuhikoOnishi, Yuki Eshita, and Masaaki Mizuno
Abstract: 2-diethylaminoethyl(DEAE)-Dextran is still an important substance for transfec-tion of nucleic acids into cultured mammalian cells by the reason of its safety owing to autoclave sterilization different from lipofection vectors. However,DEAE-Dextran may not be superior to lipofection vectors with cytotoxic and a transfection efficiency. A stable soap-less latex of 2-diethylaminoethyl(DEAE)-Dextran-methylmethacry-late(MMA) graft copolymer(DDMC)of a high transfection activity has been developed as Non-viral gene delivery vectors possible to autoclave at 121 for 15minutes. Transfection activity determined by the X-galstaining method show a higher value of 50 times or more for DDMC samples than for the starting DEAE-dextranhydrochlo-ride and a low cytotoxic is observed for DDMC. DDMC has been also observed to have a high protection facility for DNase degradation. The resulted DDMC on grafted MMA,to form a polymermicelle of Core-Shell particle, should become a stable latex with a hydrophilic-hydrophobic micro-separated-domain. The complex by DDMC/DNA may be formed initially on the stable spherical structure of the amphiphilicmicro-separated-domain of DDMC and have a good affinity to cell membrane for the endocytosis. The stronger infrared absorption spectrum shift to a high energy direction at around 3450 cm−one of the complexes between DNA and DDMC compared with DEAE-D extran may mean to form more compact structures not only by a coulomb force between the phosphoric acid of DNA and the diethyl-amino-ethyl (DEAE) group of DEAE-Dextran copolymer but also by a force from multi-inter-molecule hydrogen bond. It should conclude to DNA condensation by these inter-molecular multi-forces to be possible the higher transfection efficiency. The complex should be formed following Michaelis-Menten type equation such as complex = K1(DNA)(DDMC). It should be supported that DDMC has a strong adsorbing power with DNA because of not only its cationic property but also its hydrophobic bond and hydrogen bond. The high efficacy of this graft-copolymer autoclave-sterilized for transfection can make it a valuable tool for a safety gene delivery.
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