Edaravone, a cytoprotective drug, enhances transgene expression mediated by lipoplexes in HepG2 cells and mice


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Abstract

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.

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