中文摘要：

目的 考察烷基化低分子量聚乙烯亚胺作为基因递送载体的安全性和有效性。 方法 以1-溴十二烷和分子量为1800的分枝状 PEI （bPEI1.8K）为原料，合成 bPEI1.8K-C12，并用1H-NMR 对其结构进行确认；采用 MTT 法考察 bPEI1.8K-C12的细胞毒性；红细胞溶血实验考察 bPEI1.8K-C12的生物相容性；测定bPEI1.8K-C12/DNA 复合颗粒的粒径分布和 zeta 电位；采用激光共聚焦显微镜观察 bPEI1.8K-C12/DNA 复合颗粒的细胞摄取行为；采用琼脂糖凝胶阻滞电泳考察 bPEI1.8K-C12对DNA 的固缩能力；并用荧光素酶报告基因和绿色荧光蛋白报告基因考察 bPEI1.8K-C12的体外转染效率。 结果 经1H-NMR 确认，成功合成了 bPEI1.8K-C12；MTT结果表明 bPEI1.8K-C12对人乳腺癌 MCF-7细胞的毒性与bPEI1.8K 相当；红细胞溶血实验结果表明高浓度 bPEI1.8K-C12静脉注射时具有潜在溶血性；质量比相同时，bPEI1.8K-C12/DNA 复合颗粒的平均粒径和 zeta 电位均比相应的bPEI1.8K/DNA 大；烷基化修饰后，bPEI1.8K-C12对 DNA 的固缩能力降低，MCF-7细胞对 bPEI1.8K-C12/DNA 复合颗粒的摄取效率大大增加，bPEI1.8K-C12递送报告基因质粒的体外转染效率显著高于 bPEI1.8K，甚至与 lipofectamine2000相当。 结论 bPEI1.8K-C12是一种安全高效的基因递送载体，具有较高的进一步开发前景。

英文摘要：

Objective Preliminary evaluation of the safety and efficiency of alkylated low molecular polyethylenimine as a gene delivery vector. Methods bPEI1.8K-C12 was synthesized with branch PEI （Mw 1800; bPEI1.8K） and 1-bromododecane, and structurally confirmed with 1H-NMR. Cytotoxicity and biocompatibility of bPEI1.8K-C12 were evaluated by MTT method and hemolysis assay, respectively. Size distribution and zeta potential of bPEI1.8K-C12/DNA polyplexes were determined, and cellular uptake of the DNA polyplexes was visualized with confocal laser scanning microscope （CLSM）. DNA condensation ability of bPEI1.8K-C12 was studied by gel retardation assay, and in vitro gene delivery efficiency was investigated with luciferase and green fluorescent protein reporter gene, respectively. Results bPEI1.8K-C12 was successfully synthesized after confirmation by 1H-NMR. Cytotoxicity of bPEI1.8K-C12 on MCF-7 cells was as low as bPEI1.8K, and systematic delivery of high dose bPEI1.8K-C12 may cause hemolysis in vivo. The average size of bPEI1.8K-C12/DNA polyplexes was bigger than that of bPEI1.8K/DNA polyplexes at the same weight ratio, and the zeta potential of bPEI1.8K-C12/DNA polyplexes was higher than that of bPEI1.8K/DNA polyplexes at the same weight ratio. After alkylation, the DNA condensation ability of bPEI1.8K-C12 was reduced, but the cellular uptake of bPEI1.8K-C12/DNA polyplexes was greatly enhanced. In vitro gene transfection efficiency of bPEI1.8K-C12/DNA was significantly higher than that of bPEI1.8K, and was comparable to that of lipofectamine2000. Conclusion bPEI1.8K-C12 is a safe and efficient gene delivery vector, and holds great promise for further development.