Physicochemical Properties and Biological Performance of Polymethacrylate Based Gene Delivery Vector Systems: Influence of Amino Functionalities

Physicochemical characteristics and biological performance of polyplexes based on two identical copolymers bearing tertiary amino or quaternary ammonium groups are evaluated and compared. Poly(2-(dimethylamino)ethyl methacrylate)-b-poly(oligo(ethylene glycol) methyl ether methacrylate) block copolymer (PDMAEMA-b-POEGMA) is synthesized by reversible addition fragmentation chain transfer polymerization. The tertiary amines of PDMAEMA are converted to quaternary ammonium groups by quaternization with methyl iodide. The two copolymers spontaneously formed well-defined polyplexes with DNA. The size, zeta potential, molar mass, aggregation number, and morphology of the polyplex particles are determined. The parent PDMAEMA-b-POEGMA exhibits larger buffering capacity, whereas the corresponding quaternized copolymer (QPDMAEMA-b-POEGMA) displays stronger binding affinity to DNA, yielding invariably larger in size and molar mass particles bearing greater number of DNA molecules per particle. Experiments revealed that QPDMAEMA-b-POEGMA is more effective in transfecting pEGFP-N1 than the parent copolymer, attributed to the larger size, molar mass, and DNA cargo, as well as to the effective cellular traffic, which dominated over the enhanced ability for endo-lysosomal escape of PDMAEMA-b-POEGMA.

Automated summary

The physicochemical characteristics and biological performance of polyplexes based on two identical copolymers bearing tertiary amino or quaternary ammonium groups were evaluated and compared. The quaternized copolymer exhibited stronger binding affinity to DNA, resulting in larger particles carrying more DNA molecules per particle, and showed higher transfection efficiency in comparison to the parent copolymer.