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聚酰胺-胺树枝状大分子和油酸功能化石墨烯作为生物相容性高效基因传递载体

Polyamidoamine dendrimer and oleic acid-functionalized graphene as biocompatible and efficient gene delivery vectors.

作者信息

Liu Xiahui, Ma Dongmei, Tang Hao, Tan Liang, Xie Qingji, Zhang Youyu, Ma Ming, Yao Shouzhuo

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.

出版信息

ACS Appl Mater Interfaces. 2014 Jun 11;6(11):8173-83. doi: 10.1021/am500812h. Epub 2014 May 30.

Abstract

Functionalized graphene has good potential in biomedical applications. To address a better and multiplex design of graphene-based gene vectors, the graphene-oleate-polyamidoamine (PAMAM) dendrimer hybrids were synthesized by the oleic acid adsorption and covalent linkage of PAMAM dendrimers. The micromorphology, electrical charge property, and amount of free amine groups of the graphene-oleate-PAMAM hybrids were characterized, and the peripheral functional groups were identified. The PAMAM dendrimers could be tethered onto graphene surface in high density. The graphene-oleate-PAMAM hybrids exhibit relatively good dispersity and stability in aqueous solutions. To evaluate the potential application of the hybrids in gene delivery vectors, cytotoxicity to HeLa and MG-63 cells and gene (plasmid DNA of enhanced green fluorescent protein) transfection capacity of the hybrids were investigated in detail. The graphene-oleate-PAMAM hybrids show mammalian cell type- and dose-dependent in vitro cytotoxicity. Under the optimal condition, the hybrids possess good biocompatibility and gene transfection capacity. The surface modification of graphene with oleic acid and PAMAM improves the gene transfection efficiency 13 times in contrast to the ultrasonicated graphene. Moreover, the hybrids show better transfection efficiency than the graphene oxide-PAMAM without the oleic acid modification.

摘要

功能化石墨烯在生物医学应用中具有良好的潜力。为了实现基于石墨烯的基因载体更好的多重设计,通过油酸吸附和聚酰胺 - 胺(PAMAM)树枝状大分子的共价连接合成了石墨烯 - 油酸 - PAMAM树枝状大分子杂化物。对石墨烯 - 油酸 - PAMAM杂化物的微观形态、电荷性质和游离胺基数量进行了表征,并确定了其外围官能团。PAMAM树枝状大分子可以高密度地连接到石墨烯表面。石墨烯 - 油酸 - PAMAM杂化物在水溶液中表现出相对较好的分散性和稳定性。为了评估该杂化物在基因递送载体中的潜在应用,详细研究了其对HeLa和MG - 63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。石墨烯 - 油酸 - PAMAM杂化物表现出哺乳动物细胞类型和剂量依赖性的体外细胞毒性。在最佳条件下,该杂化物具有良好的生物相容性和基因转染能力。与超声处理的石墨烯相比,用油酸和PAMAM对石墨烯进行表面修饰可将基因转染效率提高13倍。此外,该杂化物比未经油酸修饰的氧化石墨烯 - PAMAM表现出更好的转染效率。

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