Transfection efficiency of cationic lipids with different hydrophobic domains in gene delivery

The structure of cationic lipids is a major factor for their transfection activity. A cationic lipid generally contains four functional domains: a hydrophilic headgroup, a linker, a backbone domain, and a hydrophobic domain. The structure of the hydrophobic domain determines the phase transition temperature and the fluidity of the bilayer and influences the stability of liposomes, the DNA protection from nucleases, the endosomal escape, the DNA release from complex, and the nuclear penetration. Also, toxicity of the lipids is influenced by the hydrophobic domain. The compounds used for gene delivery are classified according to the structure of the hydrophobic domain as follows: aliphatic chains, steroid domain, and fluorinated domain. In this review, we summarized recent research results concerning the structures of the hydrophobic domain, in order to find the effect of the hydrophobic domain on transfection efficiency. Understanding these would be very important for scientists to prepare novel cationic lipids and design novel formulations with high transfection efficiency.