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氧化还原调控的甲氧基聚乙二醇-二硫键-聚乙烯亚胺非病毒基因载体的研制 被引量：2

Preparation of Redox Sensitive Methoxy Poly(ethylene glycol)-SS-polyethylenimine as a Non-viral Gene Delivery Vector
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摘要 合成了氧化还原调控的甲氧基聚乙二醇-二硫键-聚乙烯亚胺[methoxy poly(ethylene glycol)-SS-polyethylenimine,mPEG-SS-PEI]。采用薄层色谱验证了该聚合物中二硫键的存在。琼脂糖凝胶电泳结果显示,mPEG-SS-PEI-pEGFP复合物在含10%胎牛血清的DMEM细胞培养液中稳定。透射电镜观察表明,不含二硫键的mPEG-PEI及mPEG-SS-PEI与pEGFP复合物的粒径均约为200 nm。体外转染试验中,荧光显微镜定性及流式细胞定量结果均表明,与mPEG-PEI-pEGFP相比,mPEG-SS-PEI-pEGFP能显著提高对U87细胞的转染效率。原因是mPEG-SS-PEI-pEGFP复合物进入细胞后能在较高浓度谷胱甘肽的还原下脱去PEG,从而恢复PEI的质子泵效应。并且,聚合物中加入二硫键未显著增加PEG化PEI的体外细胞毒性。 The redox sensitive methoxy poly （ethylene glycol）-SS-polyethylenimine （mPEG-SS-PEI） was successfully synthesized, and the disulfide bond in the above polymer was characterized by TLC. The results of agarose gel electrophoresis showed that the mPEG-SS-PEI-pEGFP complex was stable in DMEM containing 10%0 fetal bovine serum. The transmission electron microscope observation showed that the particle size of the disulfide bond-free mPEG- PEI-pEGFP complex and mPEG-SS-PEI-pEGFP complex were both about 200 nm. Moreover, the transfection efficiency of mPEG-PEI-pEGFP complex and mPEG-SS-PEI-pEGFP complex in U87 cells were determined by fluorescence microscopy and FACS flow cytometry. The qualitative and quantitative test results indicated that the transfection efficiency of mPEG-SS-PEI-pEGFP in U87 cells was significantly enhanced in comparison with that of mPEG-PEI- pEGFR It could be contributed to the PEG fraction was broken from the mPEG-SS-PEI-pEGFP complex by reduction under the high concentration of glutathione in cells, so that the proton pump effect of PEI was restored. Further, the in vitro cytotoxicity of the polymer containing disulfide bond was not significantly increased compared with the mPEG-PEI.
作者 雷杨 王晶 李莹 陆伟跃 刘敏
机构地区 复旦大学药学院药剂教研室
出处 《中国医药工业杂志》 CAS CSCD 北大核心 2012年第11期917-922,共6页 Chinese Journal of Pharmaceuticals
关键词 聚乙烯亚胺 聚乙二醇 二硫键 谷胱甘肽 基因转染 非病毒基因载体 制备 polyethylenimine poly （ethylene glycol） disulfide bond glutathione gene transfection non-viral gene delivery vector preparation
分类号 TQ460.4 [化学工程—制药化工]
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参考文献10

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二级参考文献10

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共引文献5

同被引文献38

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中国医药工业杂志
2012年 第11期

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