PEG-b-PLL的合成及其自组装纳米基因载体的研究  

The studies on PEG-b-PLL copolymer synthesis and self-assemble nano-gene vector

作　　者：孙晓利[1] 宋继斌[2] 刘东华[1] 李鹏[1] 鲁在君[2] 张娜[1] 

机构地区：[1]山东大学药学院药物制剂研究所,山东济南250012 [2]山东大学化学与化工学院高分子研究所,山东济南250100

出　　处：《中国生化药物杂志》2010年第5期302-305,309,共5页Chinese Journal of Biochemical Pharmaceutics

基　　金：山东省自然科学基金(ZR2009CM011);教育部新世纪优秀人才支持计划(NCET-08-0334)

摘　　要：目的合成两嵌段聚乙二醇-b-聚赖氨酸共聚物(PEG-b-PLL),并评价PEG-b-PLL载基因纳米复合物。方法以端氨基PEG引发Lys(z)-NCA,首先得到两嵌段共聚物PEG-b-PZLL,然后酸解去除苄氧羰基保护基团,得到了两嵌段共聚物PEG-b-PLL。通过正负电荷吸附作用自组装形成PEG-b-PLL载基因纳米复合物,考察其性质。结果制备的PEG-b-PLL载基因纳米复合物外观圆整,呈类球形,大小均匀,平均粒径为(150.3±5.5)nm,其Zeta电位为(-15.82±2.34)mV。该复合物在血浆中稳定,具有一定的抗核酸酶降解能力,且能成功的转染HepG2细胞。结论该复合物是一种制备工艺简单,性能良好,极富潜力的非病毒基因载体。Purpose To synthesize block copolymer Poly（ethylene glycol）-block-Poly（L-lysine）（PEG-b-PLL）,to prepare the PEG-b-PLL and pDNA self-assemble nano-complex and to investigate the potential of the self-assemble nano-complex as a novel gene delivery carrier.Methods The block copolymers PEG-b-PZLL were synthesized by the ring-opening polymerization of Lys（z）-NCA onto amine-terminated PEG,and then by acidolysis to remove benzyloxycarbonyl to obtain PEG-b-PLL.The PEG-b-PLL and pDNA self-assemble into nano-complex through electrostatic interactions between the negative phosphates along the pDNA backbone and positive charges displayed on PLL.The properties were evaluated.Results The obtained pDNA loaded PEG-b-PLL nano-complexes were approximately spherical in shape with average particle size of（150.3±5.5）nm and Zeta potentials of（-15.82±2.34）mv.The nano-complex could protect pDNA from plasma and nuclease degradation in vitro.It showed a low cytotoxicity to HepG2 cells and the results of the gene transfection experiment in vitro suggested that the self-assemble nano-complex could transfer the loaded gene into HepG2 cells,and the gene could express well inside the cells.Conclusion pDNA loaded PEG-b-PLL self-assemble nano-complex could be prepared easily with excellent characteristics and would be a promising non-viral gene vectors.

关 键 词：基因治疗 PEG-b-PLL 纳米复合物 非病毒基因载体 

分 类 号：R944.9[医药卫生—药剂学]