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.
出处
《中国生化药物杂志》
CAS
CSCD
北大核心
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)
