Synthesis and characterization of a pH-sensitive shielding system for polycation gene carriers  

作　　者：XIA JiaLiang1,2,CHEN Jie1,TIAN HuaYu1 & CHEN XueSi1 1Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied Chemistry,Chinese Academy of Sciences,Changchun 130022,China 2Graduate University of Chinese Academy of Sciences,Beijing 100049,China 

出　　处：《Science China Chemistry》2010年第3期502-507,共6页中国科学（化学英文版）

基　　金：supported by the National Natural Science Foundation of China (Grant Nos 20604028,50873102,50733003,A3 Foresight Program 20621140369);Ministry of Science and Technology of China (Grant No 2007DFR5020)

摘　　要：To increase the in vivo stability of polycation gene carriers,a pH-sensitive shielding system,γ-benzyl L-glutamate-co-glutamate acid polymer(PGA(60)(60 refers to the molar ratio of glutamate acid in the polymer)),was synthesized and characterized.PGA(60) showed pH sensitivity at about pH 6.0.PGA(60) shielded the positive charge of DNA/PEI(1:1) complexes.Gel retardation assay showed that no DNA-strand exchange with PGA(60) occurred after PGA(60) was added to DNA/PEI complexes at different proportions.MTT cytotoxicity tests demonstrated that neither PGA(60) nor DNA/PEI/PGA(60) ternary complexes had cytotoxicity at the test concentration.The transfection efficiency was improved when the positive charge was partly shielded by PGA(60).Because of the charge repulsion between the surface of cells and ternary complex particles,there was almost no transfection efficiency when the zeta potential of ternary complexes turned to negative.Because of the suitable pH sensitive range,PGA(60) may be a potential shielding system for polycation gene carriers to be used in vivo.To increase the in vivo stability of polycation gene carriers,a pH-sensitive shielding system,γ-benzyl L-glutamate-co-glutamate acid polymer(PGA(60)(60 refers to the molar ratio of glutamate acid in the polymer)),was synthesized and characterized.PGA(60) showed pH sensitivity at about pH 6.0.PGA(60) shielded the positive charge of DNA/PEI(1:1) complexes.Gel retardation assay showed that no DNA-strand exchange with PGA(60) occurred after PGA(60) was added to DNA/PEI complexes at different proportions.MTT cytotoxicity tests demonstrated that neither PGA(60) nor DNA/PEI/PGA(60) ternary complexes had cytotoxicity at the test concentration.The transfection efficiency was improved when the positive charge was partly shielded by PGA(60).Because of the charge repulsion between the surface of cells and ternary complex particles,there was almost no transfection efficiency when the zeta potential of ternary complexes turned to negative.Because of the suitable pH sensitive range,PGA(60) may be a potential shielding system for polycation gene carriers to be used in vivo.

关 键 词：GENE delivery SHIELDING SYSTEM PH-SENSITIVE polyglutamate 

分 类 号：O631.3[理学—高分子化学]