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Gene-therapy Inspired Polycation Coating for Protection of DNA Origami Nanostructures
Published on: January 19, 2019
Structural mediation on polycation nanoparticles by sulfadiazine to enhance DNA transfection efficiency and reduce
Xingwen Long1, Zhihui Zhang2, Shangcong Han1
1†Department of Polymer Science and Technology and Key Laboratory of Systems Bioengineering of the Ministry of Education; Department of Polymer Science and Technology, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
Abstract:
Reducing the toxicity while maintaining high transfection efficiency is an important issue for cationic polymers as gene carriers in clinical application. In this paper, a new zwitterionic copolymer, polycaprolactone-g-poly(dimethylaminoethyl methyacrylate-co-sulfadiazine methacrylate) (PC-SDZ) with unique pH-sensitivity, was designed and prepared. The incorporation of sulfadiazine into poly(dimethylaminoethyl methacrylate) (PDMAEMA) chains successfully mediates the surface properties including compacter shell structure, lower density of positive charges, stronger proton buffer capability, and enhanced hydrophobicity, which lead to reduction in toxicity and enhancements in stability, cellular uptake, endosome escape, and transfection efficiency for the PC-SDZ2 nanoparticles (NPs)/DNA complexes. Excellent transfection efficiency at the optimal N/P ratio of 10 was observed for PC-SDZ2 NPs/DNA complexes, which was higher than that of the commercial reagent-branched polyethylenimine (PEI). The cytotoxicity was evaluated by CCK8 measurement, and the results showed significant reduction in cytotoxicity even at high concentration of complexes after sulfadiazine modification. Therefore, this work may demonstrate a new way of structural mediation of cationic polymer carriers for gene delivery with high efficiency and low toxicity.
