The research explores the dual role of cationic liposomes, particularly those comprised of DOTMA:Chol (50:50), in gene therapy and their associated toxic side effects. Cationic liposomes have shown promise in delivering nucleic acids into cells, offering a non-viral vector alternative with lower immunogenicity and high reproducibility. However, the toxicity of permanently charged cationic lipids limits their in vivo application due to dose-limiting side effects, such as the induction of reactive oxygen species (ROS) leading to cell damage. The study investigates the potential of edaravone, a low-molecular-weight antioxidant drug, to mitigate these toxic effects. Despite the initial hypothesis that edaravone could counteract the cytotoxicity of DOTMA-based cationic liposomes, short-term co-administration did not prevent cytotoxicity in mouse macrophage-like RAW264.7 cells. This was attributed to the immediate necrotic cell death caused by the destabilization of the plasma membrane upon exposure to high concentrations of cationic lipids. Interestingly, prolonged exposure to edaravone following liposome treatment significantly improved cell viability, suggesting the antioxidant's ability to suppress ROS-induced apoptosis rather than preventing immediate necrotic cell death. The findings underscore the complexity of using cationic liposomes for therapeutic applications and highlight the potential of combining these with ROS scavengers like edaravone for enhancing drug efficacy while minimizing toxicity. This innovative approach could pave the way for safer and more effective delivery of genetic therapies, albeit further in vivo studies are warranted to fully ascertain the clinical viability of such combinations.
Terada, T., Kulkarni, J. A., et al. Protective effect of edaravone against cationic lipid-mediated oxidative stress and apoptosis. Biological and Pharmaceutical Bulletin. 2021, 44(1): 144-149.
For Research Use Only. Not For Clinical Use