Hepatic gene delivery system electrostatically assembled with glycyrrhizin.
Hepatic gene delivery system electrostatically assembled with glycyrrhizin.
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肝基因传递系统与甘草甜素静电组装。
DOI：
10.1021/mp400398f
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Sasaki H
中科院分区：
文献类型：
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作者：
Kurosaki T;Kawanabe S;Kodama Y;Fumoto S;Nishida K;Nakagawa H;Higuchi N;Nakamura T;Kitahara T;Sasaki H
本研究利用静电法将pDNA与聚乙烯亚胺（PEI）形成的阳离子复合物包被于明胶（GL）上，构建了一种新型的肝靶向基因传递载体。三元复合物pDNA/PEI/GL具有约100 nm的带负电荷表面的稳定颗粒。pDNA/PEI/GL在人肝癌细胞系HepG 2中的表达与pDNA/PEI复合物（pDNA/PEI）相当，无细胞毒性和凝集作用。将pDNA/PEI/GL静脉注射到小鼠体内后，在肝脏中观察到最高的基因表达。pDNA/PEI/GL在实质细胞中的基因表达显著高于非实质细胞。在这些结果的基础上，我们评价了包括编码胰岛素的pDNA（pCMV-Ins）的三元复合物的药理活性。pCMV-Ins/PEI/GL在静脉注射给小鼠后24 h降低血糖浓度。pDNA、PEI和GL的三元复合物可能是一种有前途的肝靶向基因载体。
In this study, a novel liver-targeted gene delivery vector was developed by electrostatically coating the cationic complex of pDNA and polyethylenimine (PEI) with glycyrrhizin (GL). The ternary complex, pDNA/PEI/GL, had approximately 100 nm stable particles with a negative charge surface. pDNA/PEI/GL showed high gene expression comparable to that of the complex of pDNA and PEI (pDNA/PEI) in human hepatoma cell line HepG2 without cytotoxicity and agglutination. After intravenous injection of pDNA/PEI/GL into mice, the highest gene expression was observed in the liver. pDNA/PEI/GL showed significantly higher gene expression in parenchymal cells than in nonparenchymal cells. On the basis of these results, we evaluated the pharmacological activity of the ternary complex including the pDNA encoding insulin (pCMV-Ins). The pCMV-Ins/PEI/GL decreased blood glucose concentrations 24 h after its intravenous administration to mice. The ternary complex of pDNA, PEI, and GL may be a promising liver-targeted gene vector.