α-Tocopherol-based cationic amphiphiles with a novel pH sensitive hybrid linker for gene delivery

摘要: Endosomal escape is one of the barriers for efficient liposomal gene delivery. To address this and based on earlier encouraging results using tocopherol cationic lipids, we elaborated chemical modifications lipids by introducing a novel hybrid pH sensitive linker “ether-β-hydroxy-triazole” between tocopherol, anchoring moiety basic tris(2-hydroxy ethyl)quaternary ammonium head group (Lp2). As control designed two (Lp1 Lp3), with only ether-β-hydroxy in α-tocopherol quaternary tris(2-hydroxyethyl)ammonium (Lp1) other same i.e. linked tris-ethyl (Lp3). Liposomes were formulated combination well-known co-lipid, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) biophysical characteristics such as DNA binding, hydrodynamic diameters global surface charges liposomes lipoplexes respective evaluated. Cell viability assay vitro transfection studies carried out NIH3 T3, B16F10, HEK-293, HepG2 cell lines. In data (Lp1, Lp2 Lp3) revealed that lipid showed superior efficiency when compared remaining analogues. More importantly, has shown similar pattern HEK-293 lines commercially available Lipofectamine 3000.