Design, Synthesis, and inVitro Transfection Biology of Novel Tocopherol Based Monocationic Lipids: A Structure−Activity Investigation

Abstract

Herein, we report on the design, synthesis, and in vitro gene delivery efficacies of five novel tocopherol based cationic lipids (1-5) in transfecting CHO, B16F10, A-549, and HepG2 cells. The in vitro gene transfer efficiencies of lipids (1-5) were evaluated by both β-galactosidase reporter gene expression and inverted fluorescent microscopic experiments. The results of the present structure-activity investigation convincingly demonstrate that the tocopherol based lipid with three hydroxyl groups in its headgroup region showed 4-fold better transfection efficiency than the commercial formulation. The results also demonstrate that these tocopherol based lipids may be targeted to liver. Transfection efficiency of all the relevant lipids was maintained even when the serum was present during the transfection conditions. The results indicated that the designed systems are quite capable of transferring the DNA into all four types of cells studied with low or no toxicity.

trans-2-Aminocyclohexanol-based amphiphiles as highly efficient helper lipids for gene delivery by lipoplexes

“…All the prepared lipoplexes carried excess positive surface charges as indicated by the positive ζ-potential values ( Table 2). Generally all the lipoplexes decreased in ζ-potential values and increased in size as compared to the corresponding cationic liposomes, which is consistent with other studies of cationic lipoplex-mediated transfection [33,50]. The hydrodynamic diameter of the lipoplexes ranges between 190 and 380 nm.…”

Synthetic vectors for gene delivery: An overview of their evolution depending on routes of administration.

“…It has been demonstrated that DOPC is a more efficient colipid compared to DOPE [30]. Indeed, with DOPE the internalization of the resulting complexes takes place principally by fusogenic interactions between the complexes and membranes, while in the presence of DOPC endocytosis facilitates lipoplex uptake [30]. Subsequently a variety of polycationic lipid analogues have been developed.…”

Biotinylated Cyclen‐Contained Cationic Lipids as Non‐Viral Gene Delivery Vectors

“…We speculate that the relatively higher DNA‐binding ability and lower cytotoxicity of 5c may benefit its transfection behavior. It is also reported recently that α‐tocopherol‐containing lipids showed high gene delivery efficiency and low cytotoxicity . Although the transfection efficiency was still lower than commercially available lipofectamine 2000, these results further revealed the superiority of α‐tocopherol as hydrophobic moiety in cationic lipid structure for non‐viral transfection.…”