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通过聚酰胺-胺树枝状大分子和甘草次酸的共价连接来改善氧化石墨烯的分散性、生物相容性和靶向基因转染。

Improving dispersive property, biocompatibility and targeting gene transfection of graphene oxide by covalent attachment of polyamidoamine dendrimer and glycyrrhetinic acid.

机构信息

Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha 410081, People's Republic of China.

Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education), College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha 410081, People's Republic of China; College of Science, Central South University of Forestry and Technology, Changsha 410004, People's Republic of China.

出版信息

Colloids Surf B Biointerfaces. 2018 Nov 1;171:622-628. doi: 10.1016/j.colsurfb.2018.07.067. Epub 2018 Jul 30.

Abstract

The surface functional groups of GO have significant effects on the performances of GO-based gene delivery vector. In this work, the polyamidoamine (PAMAM) dendrimer and glycyrrhetinic acid (GA) were tethered onto the GO surface by one-step covalently cross-linking method. The micro-morphology, surface functional groups, and zeta potential of the obtained GO-PAMAM-GA hybrid were characterized and verified. The effects of GA amount in the hybrid on the dispersive property in cell culture medium, in vitro cytotoxicity to human hepatocarcinoma (SMMC-7721) and human embryonic kidney (HEK-293) cells, and gene (plasmid DNA of enhanced green fluorescent protein) transfection capacity were investigated in detail. Under optimal conditions, the obtained hybrid shows small average size (about 160 nm) and has very good dispersive stability (in 30 days) in cellular culture medium. Compared with the GO-PAMAM without GA modification, the GO-PAMAM-GA hybrid exhibits greatly enhanced biocompatibility to the two cell lines. The cellular viability of SMMC-7721 cells still retains about 98% even the concentration of the hybrid up to 200 μg mL. The gene transfection capacity of the GO-PAMAM has been improved about 50% through the GA functionalization. Moreover, the GO-PAMAM-GA hybrid possesses targeting gene transfection to SMMC-7721 cells.

摘要

GO 的表面官能团对基于 GO 的基因传递载体的性能有显著影响。在这项工作中,通过一步共价交联法将聚酰胺-胺(PAMAM)树枝状大分子和甘草次酸(GA)接枝到 GO 表面。对所得 GO-PAMAM-GA 杂化物的微观形貌、表面官能团和 Zeta 电位进行了表征和验证。详细研究了杂化物中 GA 含量对其在细胞培养液中的分散性、体外对人肝癌(SMMC-7721)和人胚肾(HEK-293)细胞的细胞毒性以及基因(增强型绿色荧光蛋白的质粒 DNA)转染能力的影响。在最佳条件下,所得杂化物的平均粒径较小(约 160nm),在细胞培养液中的分散稳定性非常好(30 天)。与未修饰 GA 的 GO-PAMAM 相比,GO-PAMAM-GA 杂化物对两种细胞系表现出更好的生物相容性。即使杂化物的浓度高达 200μgmL,SMMC-7721 细胞的细胞活力仍保持在 98%左右。通过 GA 功能化,GO-PAMAM 的基因转染能力提高了约 50%。此外,GO-PAMAM-GA 杂化物具有针对 SMMC-7721 细胞的靶向基因转染能力。

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