Biscarbamate cross-linked polyethylenimine derivative with low molecular weight, low cytotoxicity, and high efficiency for gene delivery
Polyethylenimine (PEI), especially PEI 25 kDa, has been widely studied for deliveryof nucleic acid drugs both in vitro and in vivo. However, it lacks degradable linkages and istoo toxic for therapeutic applications. Hence, low-molecular-weight PEI has been explored asan alternative to PEI 25 kDa. To reduce cytotoxicity and increase transfection efficiency, wedesigned and synthesized a novel small-molecular-weight PEI derivative (PEI-Et, Mn: 1220,Mw: 2895) with ethylene biscarbamate linkages. PEI-Et carried the ability to condense plasmidDNA (pDNA) into nanoparticles. Gel retardation assay showed complete condensationof pDNA at w/w ratios that exceeded three. The particle size of polymer/pDNA complexeswas between 130 nm and 180 nm and zeta potential was 5–10 mV, which were appropriatefor cell endocytosis. The morphology of PEI-Et/pDNA complexes observed by atomic forcemicroscopy (AFM) was spherically shaped with diameters of 110–190 nm. The transfectionefficiency of polymer/pDNA complexes as determined with the luciferase activity assay as wellas fluorescence-activated cell-sorting analysis (FACS) was higher than commercially availablePEI 25 kDa and Lipofectamine 2000 in various cell lines. Also, the polymer exhibited significantlylower cytotoxicity compared to PEI 25 kDa at the same concentration in three cell lines.Therefore, our results indicated that the PEI-Et would be a promising candidate for safe andefficient gene delivery in gene therapy.
gene delivery, polyethylenimine, nanoparticles, cytotoxicity, transfectionefficiency
Yu-Qiang Wang Jing Su Fei Wu Ping Lu Li-Fen Yuan Wei-En Yuan Jing Sheng Tuo Jin
Department of Geriatrics,Shanghai Ninth People”s Hospital Affiliated to Shanghai Jiao Tong Universit School of Pharmacy,Shanghai Jiao Tong University,Shanghai,People”s Republic of China School of Pharm School of Pharmacy,Shanghai Jiao Tong University,Shanghai,People”s Republic of China Department of Geriatrics,Shanghai Ninth People”s Hospital Affiliated to Shanghai Jiao Tong Universit
国内会议
2012上海市研究生学术论坛暨第三届上海交通大学医(理)工研究生学术论坛
上海
英文
1-12
2012-08-15（万方平台首次上网日期，不代表论文的发表时间）