Objective To synthesize a biodegradable non-viral gene carrier with a high transfection efficiency and a low cytotoxicity. Methods Poly(ethylene glycol)- block- (poly(L- glutamic acid)- graft- polyethylenimine) was prepared via ammonolysis of poly(ethylene glycol)-block-poly (γ-benzyl L-glutamate) with the low-molecular-mass polyethylenimine (600 Da). The synthesized copolymer was characterized by 1H nuclear magnetic resonance spectroscopy and gel permeation chromatography. The polyplex micelle from PEG-b-(PG-g-PEI) and plasmid DNA (pDNA) was studied using dynamic light scattering, zeta-potential measurements, and gel retardation assay. The in vitro cytotoxicity and transfection efficiency of PEG-b-(PG-g-PEI) were tested by MTT assay and luciferase assay in HEK 293T cells using PEI (25 kDa) as the control. Results PEG-b-(PG-g-PEI) could efficiently condense DNA into nanosized particles with positive surface charges when the N/P ratio of polymer and DNA was above 5:1. The zeta potential of the polyplexes was about 25 mV, and the particle size was 120 nm at a N/P ratio of 10. The cell toxicity and gene transfection evaluations showed a lower cytotoxicity and a higher gene transfection efficiency of the copolymer than PEI 25000 in HEK 293T cells. Conclusions The polymer can be used as a potential non-viral gene carrier for gene therapy.%目的：结合重组低分子量PEI和PEG结构修饰两种手段合成出新型可生物降解的非病毒基因载体聚乙二醇-b-(聚谷氨酸-g-聚乙烯亚胺)。方法用相对分子质量600的聚乙烯亚胺氨解嵌段聚合物PEG-b-PBLG，合成非病毒基因载体聚乙二醇-b-(聚谷氨酸-g-聚乙烯亚胺)；利用核磁共振氢谱、凝胶渗透色谱、激光粒度分析仪、zeta电位仪和凝胶电泳对载体及其与DNA复合物进行了表征，并通过体外细胞实验考察了载体的细胞毒性与转染效率。结果我们成功合成出窄分布的非病毒基因载体聚乙二醇-b-(聚谷氨酸-g-聚乙烯亚胺)；凝胶电泳测定结果表明当N/P比大于5时载体能很好地包裹DNA；载体与DNA形成的复合物粒径为120 nm，zeta电位25 mV；通过MTT实验和体外质粒转染实验显示出载体在测量范围内具有极低的细胞毒性和很高的转染效率。结论聚合物聚乙二醇-b-(聚谷氨酸-g-聚乙烯亚胺)有望作为非病毒基因传递载体。
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