Scaling the effect of hydrophobic chain length on gene transfer properties of di-alkyl, di-hydroxy ethylammonium chloride based cationic amphiphiles

摘要: The success of gene therapy critically depends on the availability efficient transfection vectors. Cationic lipids are most widely studied non-viral molecular architecture cationic lipid determines its efficiency. Variations in alkyl chain lengths influence self-assembly and liposomal fusion with cell membrane. These factors determine ability lipid. Thus, to probe effect asymmetry hydrophobic chains efficiency, we designed synthesized a series by systematically varying one two linked quaternary nitrogen centre from C18 C10 keeping other constant (Lip1818-Lip1810). Transfection studies multiple cultured mammalian cells (CHO, B16F10 HeLa) revealed that C18:C14 C18:C12 (Lip1814 & Lip1812) showed 20–30% higher efficacies than their counterparts at 2 : 1 4 : 1 pDNA charge ratios. Cryo-transmission electron images unilamellar vesicle structures for liposomes lipids. Mechanistic involving Small Angle X-ray Scattering (SAXS) region has significant impact plasma membrane model. Collectively, these findings demonstrate length an important role liposome–DNA interactions optimal ratios, which turn modulates transfer properties.