title: Versatile functionalization of gene vectors via different types of zwitterionic betaine species for serum-tolerant transfection.
abstract: For ideal polymeric gene vectors, their serum stability is of crucial importance. Polycation vectors usually suffer from colloidal aggregation, which makes them easily cleared from the bloodstream. Recently, we reported a comb-shaped vector (DPD) consisting of a dextran backbone and disulfide-linked cationic poly((2-dimethyl amino)ethyl methacrylate) side chains for efficient gene delivery. In this work, versatile functionalization of DPD (as a model gene vector) was proposed via the introduction of different types of zwitterionic carboxybetaine and sulfobetaine species for improving biophysical properties. The incorporation of zwitterionic betaine did not destroy the DNA condensation capability of vectors. All the zwitterionic betaine-functionalized DPD vectors exhibited lower cytotoxicities than the pristine DPD. The DPD-b-polycarboxybetaine block copolymer (DPDbPC) exhibited better gene delivery abilities than the corresponding DPD-r-polycarboxybetaine random copolymer (DPDrPC). Moreover, in the serum case with a high concentration (30%) of fetal bovine serum, the DPD-b-polysulfobetaine block copolymer (DPDbPS) produced much higher gene transfection efficiencies than DPDbPC. Cellular internalization results indicated that the incorporation of zwitterionic betaine could benefit serum stabilities of vectors and enhance cellular uptake. The present study demonstrated that proper incorporation of zwitterionic betaine into gene carriers was an effective method to produce serum-tolerant transfection vectors.
authors.affiliation: State Key Laboratory of Chemical Resource Engineering, Key Laboratory of Carbon Fiber and Functional Polymers, Ministry of Education, College of Materials Science & Engineering, Beijing University of Chemical Technology, Beijing 100029, People's Republic of China.
authors.forename: Ke-Mao
authors.initials: KM
authors.lastname: Xiu
authors.forename: Na-Na
authors.initials: NN
authors.lastname: Zhao
authors.forename: Wan-Tai
authors.initials: WT
authors.lastname: Yang
authors.forename: Fu-Jian
authors.initials: FJ
authors.lastname: Xu
mesh_terms: D000818:Animals; D001622:Betaine / Q000737:chemistry*; D019556:COS Cells; D002522:Chlorocebus aethiops; D004337:Drug Carriers / Q000138:chemical synthesis*; D004355:Drug Stability; D005822:Genetic Vectors / Q000737:chemistry / Q000235:genetics*; D008422:Materials Testing; D010957:Plasmids / Q000008:administration & dosage / Q000737:chemistry* / Q000235:genetics*; D044967:Serum / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
chemical_list: D004337:Drug Carriers; D001622:Betaine