Physicochemical factors that influence the biocompatibility of cationic liposomes and their ability to deliver DNA to the nuclei of ovarian cancer SK-OV-3 cells

Abstract

Cationic liposomes composed of 3-[N-(N’,N’-dimethylaminoethane)-carbamoyl] cholesterol (DC-chol) and dioleoylphosphatidylethanolamine (DOPE) have previously been shown to have applications in gene delivery. Our study aims to explore the effects of inclusion of polyethylene glycol (PEG) and using different molar ratios of DC-chol/DOPE on size, zeta potential, cytotoxicity and DNA delivery of DC-chol/DOPE liposomes. Our results show that PEGylation reduces the cyto-toxicity of DC-chol/DOPE liposomes, and, furthermore, PEGylated liposome-DNA lipoplexes are smaller in size and more uniform in size distribution than those that are not PEGylated. Additionally, toxicity against ovarian cancer SKOV-3 cells decreases with the amount of cationic DC-chol present in the formulation; however, decreased delivery of DNA to cellular nuclei is also observed. Transfection with the PEGylated liposomes was successfully demonstrated using plasmid DNA with a known functional outcome. These results offer further insight into physicochemical properties important for cationic liposomes as vehicles for DNA delivery and demonstrate the potential of PEGylated DC-chol/DOPE liposomes as systemic delivery carriers for DNA-mediated ovarian cancer therapy.