Influence of Liposome Composition on Plasmid DNA Delivery to Eukaryotic Cells

Gene therapy is a promising method for the treatment of various diseases by introducing therapeutic nucleic acids, for the delivery of which cationic liposomes are widely used. This work demonstrates the ability of cationic liposomes composed of a polycationic lipid 2X3 (1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetraazahexacosane tetrahydrochloride) and helper lipid DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine) at various ratios (2.5 : 1 (L1); 2 : 1 (L2); 1.5 : 1 (L3); 1 : 1 (L4); 1 : 1.5 (L5); 1 : 2 (L6); 1 : 2.5 (L7)) to mediate the delivery of plasmid DNA (pDNA) into HEK293 cells with an efficiency higher than that of the commercial transfectant Lipofectamine 2000. We found that transfection activity of cationic liposomes depends on their composition as well as lipoplex composition (N/P ratio). Cationic liposomes were nontoxic to HEK293 cells and were more effective than Lipofectamine 2000 at the N/P ratios ≥6/1. In this case, the highest efficiency was achieved for liposomes L2. At lower N/P ratios = 1/1, 2/1, and 4/1, liposomes L1 can be used to provide targeted NA delivery into cells. Thus, for further in vivo experiments, nontoxic and small-size liposomes L1 and L2, in which the amount of lipid 2X3 was two or more times higher than that of helper lipid DOPE, were selected.