中文摘要：

为了提高基因传递效率,本研究对用于基因传递的高分子/无机杂化纳米粒子进行了多肽功能化改性.利用生物素-亲和素（biotin-avidin）作用将同时具有肿瘤靶向性的精氨酸-甘氨酸-天冬氨酸（RGD）序列和细胞穿透功能的R8序列的生物素化多肽（biotinylated peptide,BP）修饰在具有良好生物相容性的生物素化肝素/鱼精蛋白/碳酸钙/DNA（HPB/PS/CaCO_3/DNA）杂化纳米粒子表面,通过水溶液中的自组装方法制备得到了BP/Avidin/HPB/PS/CaCO_3/DNA靶向基因传递纳米粒子.测量了其粒径和Zeta电位等,考察了该基因传递纳米粒子对HeLa细胞的转染效果.结果表明,BP/Avidin/HPB/PS/CaCO_3/DNA基因传递纳米粒子的水合粒径在175nm左右,Zeta电位为负值;与未经多肽功能化的传递系统相比,该纳米粒子能更好地被细胞摄入,达到更高的转染效率,说明多肽功能化能提高杂化纳米粒子的基因传递效果;与商品化的基因转染试剂Lipofectamine 2000相比,该纳米粒子介导荧光素酶（pGL3-Luc）质粒在细胞中的表达水平明显较高.

英文摘要：

To improve the gene delivery efficiency,peptide functionalized polymer/inorganic hybrid nanoparticles for gene delivery were prepared in this study.A functional biotinylated peptide（BP）with a Arg-Gly-Asp（RGD）sequence for tumor targeting and a R8 sequence for enhanced cell uptake was introduced on the surface of heparin-biotin/protamine sulfate/calcium carbonate/DNA（HPB/PS/CaCO_3/DNA）hybrid nanoparticles with ideal biocompatibility through biotin-avidin interaction.The peptide functionalized polymer/inorganic hybrid nanoparticles（BP/Avidin/HPB/PS/CaCO_3/DNA）for targeting gene delivery were prepared by self-assembly in an aqueous medium.The size and Zeta potential of the nanoparticles were measured.The in vitro gene transfections were carried out in HeLa cells,using pGL3-Luc as a reporter plasmid.The results show that BP/Avidin/HPB/PS/CaCO_3/DNA nanoparticles have a hydrodynamic size about 175 nm with a negative Zeta potential.As compared with the system without peptide functionalization,the peptide functionalized gene delivery system results in an increased cell uptake and enhanced transfection efficiency,demonstrating that the peptide modification can significantly enhance the gene delivery efficiency.The luciferase expression mediated by the peptide functionalized hybrid nanoparticles is higher than that mediated commercialized Lipofectamine 2000.