Cyclic RGD-poly(ethylene glycol)-polyethyleneimine is more suitable for glioblastoma targeting gene transfer in vivo
Cyclic RGD-poly(ethylene glycol)-polyethyleneimine is more suitable for glioblastoma targeting gene transfer in vivo
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环状RGD-聚乙二醇-聚乙烯亚胺更适合胶质母细胞瘤体内靶向基因转移
DOI：
10.3109/1061186x.2010.542244
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发表时间：
2011-07
影响因子：
4.5
通讯作者：
钱隽
中科院分区：
文献类型：
--
作者：
占昌友;朱建华;陆伟跃;钟高仁;俸林灵;钱隽
精氨酸-甘氨酸-天冬氨酸（Arginine-glycine-asparticacid，RGD）是一种广泛选择的配体，用于提高聚乙烯亚胺（polyethyleneimine，PEI）的体内特异性基因靶向转染效率。然而，最佳的RGD缀合模式，RGD-聚（乙二醇）-PEI（RGD-PEG-PEI）或RGD-PEI-甲氧基聚（乙二醇）（RGD-PEI-mPEG）仍然存在争议。在这项研究中，RGD-PEG-PEI和RGD-PEI-mPEG的合成和比较方面的胶质母细胞瘤细胞结合能力和肿瘤靶向能力的复合物与质粒DNA。这些结果表明RGD-PEG-PEI/质粒增强型绿色荧光蛋白（pEGFP）-N2复合物与U87细胞的结合亲和力高于RGD-PEI-mPEG/pEGFP-N2复合物。在体外和体内对U87细胞进行了基因转染。在体外实验中，两种RGD修饰的PEI衍生物都在一定程度上提高了基因转染效率。然而，所有的复合物（有或没有RGD修饰）具有高转染效率。RGD-PEG-PEI/pEGFP-N2复合物在皮下胶质母细胞瘤小鼠体内的生物分布显著高于RGD-PEI-mPEG/pEGFP-N2复合物，提示其体内基因转染效率更高。在RGD-PEG-PEI中，PEG间隔基的使用特别重要。这些结果表明，RGD-PEG-PEI更适合于体内靶向基因转移。
Arginine-glycine-aspartic acid (RGD) is a widely chosen ligand to improve the specific gene targeting transfection efficiency of polyethyleneimine (PEI) in vivo. However, the optimal RGD conjugating mode, RGD-poly(ethylene glycol)-PEI (RGD-PEG-PEI) or RGD-PEI-methoxyl poly(ethylene glycol) (RGD-PEI-mPEG) still remains controversial. In this study, RGD-PEG-PEI and RGD-PEI-mPEG were synthesized and compared with respects to their glioblastoma cell-binding capability and tumor-targeting ability of their complexes with plasmid DNA. These results demonstrated that RGD-PEG-PEI/plasmid enhanced green fluorescent protein (pEGFP)-N2 complexes had higher binding affinities with U87 cells than RGD-PEI-mPEG/pEGFP-N2 complexes. The gene transfection was also performed on U87 cells in vitro and in vivo. In vitro, both of the RGD-modified PEI derivatives enhanced the gene transfection efficiency to some extent. However, all of the complexes (with or without RGD modification) had high transfection efficiency. The biodistribution of RGD-PEG-PEI/pEGFP-N2 complexes in mice bearing subcutaneous glioblastomas were significantly greater than that of RGD-PEI-mPEG/pEGFP-N2 complexes, suggesting a more efficient gene transfection in vivo. In the RGD-PEG-PEI, the use of a PEG spacer was particularly important. These results indicated that RGD-PEG-PEI was more suitable for targeted gene transfer in vivo.
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DOI：
10.1002/jgm.515
发表时间：
2004-03
期刊：
The Journal of Gene Medicine
影响因子：
--
作者：
S. Grosse;Y. Aron;Isabelle Honoré;G. Thévenot;C. Danel;A. Roche;M. Monsigny;I. Fajac
通讯作者：
S. Grosse;Y. Aron;Isabelle Honoré;G. Thévenot;C. Danel;A. Roche;M. Monsigny;I. Fajac
影响因子：
5.1
作者：
Ogris, M;Brunner, S;Wagner, E
通讯作者：
Wagner, E
影响因子：
4.5
作者：
Meng, Qinggang;Yu, Mei;Lu, Weiyue
通讯作者：
Lu, Weiyue
影响因子：
14
作者：
Suk, Jung Soo;Suh, Junghae;Hanes, Justin
通讯作者：
Hanes, Justin
影响因子：
4.2
作者：
Abdallah, B;Hassan, A;Demeneix, BA
通讯作者：
Demeneix, BA