Nonviral Plasmid DNA Carriers Based on N,N'-Dimethylaminoethyl Methacrylate and Di(ethylene glycol) Methyl Ether Methacrylate Star Copolymers

作者：Mendrek Barbara; Sieron Lukasz; Zymelka Miara Iwona; Binkiewicz Paulina; Libera Marcin; Smet Mario; Trzebicka Barbara; Sieron Aleksander L; Kowalczuk Agnieszka; Dworak Andrzej^*

来源：Biomacromolecules, 2015, 16(10): 3275-3285.

DOI：10.1021/acs.biomac.5b00948

Star polymers with random and block copolymer arms made of cationic N,N'-dimethylaminoethyl methacrylate (DMAEMA) and nonionic di(ethylene glycol) methyl ether methacrylate (DEGMA) were synthesized via atom transfer radical polymerization (ATRP) and used for the delivery of plasmid DNA in gene therapy. All stars were able to form polyplexes with plasmid DNA. The structure and size of the polyplexes were precisely determined using light scattering and cryo-TEM microscopy. The hydrodynamic radius of a complex of DNA with star was dependent on the architecture of the star arms, the DEGMA content and the number of amino groups in the star compared to the number of phosphate groups of the nucleic acid (N/P ratio). The smallest polyplexes (R-h(90 degrees) similar to 50 nm) with positive zeta potentials (similar to 15 mV) were formed of stars with N/P = 6. The introduction of DEGMA into the star structure caused a decrease of polyplex cytotoxicity in comparison to DMAEMA homopolymer stars. The overall transfection efficiency using HT-1080 cells showed that the studied systems are prospective gene delivery agents. The most promising results were obtained for stars with random copolymer arms of high DEGMA content.

• 出版日期2015-10