A series of diblock glycopolycations were created by polymerizing 2-deoxy-2-methacrylamido glucopyranose (MAG) with either a tertiary amine-containing monomer, N-[3-(N, N-dimethylamino) propyl] methacrylamide (DMAPMA), or a primary amine-containing unit, N-(2-aminoethyl) methacrylamide (AEMA). Several structures were synthesized via aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization that varied in the block lengths of MAG, DMAPMA, and AEMA. All of the structures were examined for their ability to complex plasmid DNA into polyplex structures and their ability to prevent colloidal aggregation in physiological salt conditions. Over the experimental time period, the polyplexes formed from these diblock copolymers were all stable from colloidal aggregation, according to dynamic light scattering and cryogenic transmission electron microscopy experiments. In vitro transfection experiments were performed in both HeLa (human cervix adenocarcinoma) cells and HepG2 (human liver hepatocellular carcinoma) cells to examine the role of block length on transfection efficiency and toxicity. The glycopolycation vehicles with shorter DMAPMA blocks exhibit lower cellular toxicity and higher transfection efficiency in both two cell lines than the other analogs. In addition, these analogs revealed higher cellular uptake and transfection efficiency in HepG2 cells than in HeLa cells.

Structural impact and targeting effect of diblock glycopolymer pDNA delivery system

247th National Meeting (2014)

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