Effect of the hydrocarbon chain and polymethylene spacer lengths on gene transfection efficacies of gemini lipids based on aromatic backbone

Abstract

Design, syntheses, and gene delivery efficacies of fifteen novel gemini (dimeric) and three monomeric cationic lipids anchored on an aromatic backbone have been described. Each new lipid has been used for liposome formation, and optimal formulations were used to determine the structure-activity correlation of the gene transfection efficacies of these lipids in HeLa and HT1080 cells. The results of the present investigation bring out the effect of hydrocarbon chain lengths and the length of the spacer between the headgroups on gene transfection efficiencies of the cationic gemini lipids based on aromatic backbone. The lipids bearing n-C₁₄H₂₉ hydrocarbon chain lengths have been found to be the best transfecting agents compared to their counterparts with n-C₁₆H₃₃ and n-C₁₂H₂₅chains in HeLa cells. On the other hand, in HT1080 cells, the lipids based on n-C₁₂H₂₅ and n-C₁₄H₂₉ chains were found to be more potent transfecting agents than lipids possessing n-C₁₆H₃₃ chains. Transmission electron microscopy examination revealed the existence of spherical lipid-DNA complexes.