Edaravone, a cytoprotective drug, enhances transgene expression mediated by lipoplexes in HepG2 cells and mice
Edaravone, a cytoprotective drug, enhances transgene expression mediated by lipoplexes in HepG2 cells and mice
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DOI：
10.1016/j.ijpharm.2018.06.068
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发表时间：
2018-09
影响因子：
5.8
通讯作者：
Shu Wang;S. Fumoto;Hirotaka Miyamoto;Masakazu Tanaka;K. Nishida
中科院分区：
文献类型：
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作者：
Shu Wang;S. Fumoto;Hirotaka Miyamoto;Masakazu Tanaka;K. Nishida
基因治疗的一个要求是高效的核酸输送。然而，阳离子脂质体在基因治疗中的应用受到其低效转染能力的限制，这可能是由于细胞毒性造成的。这种细胞毒性高度依赖于阳离子脂质诱导的活性氧自由基(ROS)。在这里，为了提供细胞保护，我们使用了一种有效的抗氧化药物依达拉奉，在阳离子脂质体/质粒DNA复合体(脂联体)的转染过程中清除ROS。游离伊达拉奉和载脂体能增强人肝癌细胞株HepG2的转基因表达，而载脂体能降低依达拉奉的有效剂量。依达拉奉的细胞保护作用可降低阳离子脂质体的细胞毒性。依达拉奉在商品化产品Lipoect tamine®3000中也是有效的，这可能会扩大依达拉奉的应用范围，以提高转染率。与游离依达拉奉相比，EDLPs在小鼠体内的转基因表达也更好。我们的发现将促进高效、安全的基因治疗的发展。
A requirement of gene therapy is efficient nucleic acid delivery. However, the application of cationic liposomes to gene therapy is restricted by their inefficient transfection capacity, which may be caused by cytotoxicity. This cytotoxicity is highly dependent on cationic lipid-induced reactive oxygen species (ROS). Here, to provide cellular protection, we used edaravone, an efficacious anti-oxidative drug, to scavenge ROS during transfection using cationic liposome/plasmid DNA complexes (lipoplexes). Both free edaravone and edaravone-loaded liposomes (EDLPs) enhanced transgene expression in the human hepatoma cell line, HepG2, while EDLPs decreased the effective dose of edaravone. The cellular protective effect of edaravone was found to decrease the cytotoxicity of cationic liposomes. Edaravone was also effective in the commercial product, Lipofectamine® 3000, which may expand the application of edaravone to promote transfection efficiency. Compared with free edaravone, EDLPs also showed superior transgene expression in mice. Our findings will promote the development of efficient and safe gene therapy.