Glutathione-mediated shedding of PEG layers based on disulfide-linked catiomers for DNA delivery
Glutathione-mediated shedding of PEG layers based on disulfide-linked catiomers for DNA delivery
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谷胱甘肽介导的基于二硫键连接的阳离子异构体的 PEG 层脱落用于 DNA 递送
DOI：
10.1039/c1jm11693b
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发表时间：
2011-01-01
影响因子：
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通讯作者：
Shi, Dong-Lu
中科院分区：
文献类型：
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作者：
Cai, Xiao-Jun;Dong, Hai-Qing;Shi, Dong-Lu
工程化的 PEG 可分离阳离子异构体被开发为非病毒基因载体，以响应细胞内还原环境分离 PEG 层。琼脂糖凝胶电泳和 MTT 测定证明，这些阳离子异构体表现出高 DNA 结合能力和降低的细胞毒性。在透射电子显微镜 (TEM) 下观察到，mPEG-SS-PLL/DNA 复合物的尺寸约为 100 nm，具有规则的球形形状。该复合物稳定地分散在含有10%血清的水介质中。然而，在 10 mM 谷胱甘肽 (GSH) 存在的情况下，由于 PEG 片段通过二硫键裂解而分离，观察到快速聚集。这些复合物在优化条件下在 293T 和 Hela 细胞中表现出高转染效率。实验结果表明mPEG-SS-PLL阳离子异构体作为非病毒基因载体具有广阔的应用前景。
Engineered PEG-detachable catiomers were developed as non-viral gene vectors to detach the PEG layers responsive to the intracellular reducing environment. These catiomers were found to exhibit high DNA binding ability and reduced cytotoxicity, as evidenced in agarose gel electrophoresis and MTT assays. The size of the mPEG-SS-PLL/DNA complexes was around 100 nm with a regular spherical shape, as observed under transmission electron microscopy (TEM). The complexes were stably dispersed in an aqueous medium with 10% serum. However, fast aggregation was observed in the presence of 10 mM glutathione (GSH) due to detachment of the PEG segment via disulfide cleavage. These complexes showed high transfection efficiency in 293T and Hela cells under optimized conditions. The experimental results indicated that the mPEG-SS-PLL catiomers may have promising potential as a non-viral gene vector.