title: Structural mediation on polycation nanoparticles by sulfadiazine to enhance DNA transfection efficiency and reduce toxicity.
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.
authors: †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.
authors: Xingwen
authors: X
authors: Long
authors: ∥Research Center of Basic Medical Science and Department of Immunology, Basic Medical College; Key Laboratory of Immune Microenvironment and Diseases, Ministry of Education of China; Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors: Zhihui
authors: Z
authors: Zhang
authors: †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.
authors: Shangcong
authors: S
authors: Han
authors: †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.
authors: Minjie
authors: M
authors: Tang
authors: †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.
authors: Junhui
authors: J
authors: Zhou
authors: †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.
authors: Jianhua
authors: J
authors: Zhang
authors: ∥Research Center of Basic Medical Science and Department of Immunology, Basic Medical College; Key Laboratory of Immune Microenvironment and Diseases, Ministry of Education of China; Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors: Zhenyi
authors: Z
authors: Xue
authors: ∥Research Center of Basic Medical Science and Department of Immunology, Basic Medical College; Key Laboratory of Immune Microenvironment and Diseases, Ministry of Education of China; Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors: Yan
authors: Y
authors: Li
authors: ∥Research Center of Basic Medical Science and Department of Immunology, Basic Medical College; Key Laboratory of Immune Microenvironment and Diseases, Ministry of Education of China; Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors: Rongxin
authors: R
authors: Zhang
authors: †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.
authors: Liandong
authors: L
authors: Deng
authors: †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.|§Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300072, China.
authors: Anjie
authors: A
authors: Dong
mesh_terms: D002412:Cations; D002470:Cell Survival / Q000187:drug effects; D003460:Crystallization / Q000379:methods; D004247:DNA / Q000008:administration & dosage / Q000235:genetics* / Q000633:toxicity; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D008422:Materials Testing; D008689:Methacrylates / Q000737:chemistry*; D053769:Nanocapsules / Q000737:chemistry* / Q000633:toxicity* / Q000648:ultrastructure; D009757:Nylons / Q000737:chemistry*; D013411:Sulfadiazine / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
chemical_list: D002412:Cations; D008689:Methacrylates; D053769:Nanocapsules; D009757:Nylons; C407037:poly(2-(dimethylamino)ethyl methacrylate); D013411:Sulfadiazine; D004247:DNA
keywords: DNA delivery; cytotoxicity; pH sensitivity; sulfadiazine; transfection efficiency