α-Tocopherol-Conjugated, Open Chain Sugar-Mimicking Cationic Lipids: Design, Synthesis and In-Vitro Gene Transfection Properties

Sugar based cationic lipids are promising carriers of nucleic acids into various cells. Particularly, abundant hydroxyl functional groups in the sugar-like moieties are believed to enhance target oriented uptake as well as biocompatibility. Towards this direction, we have synthesized three new cationic lipid analogues with or without sugar-like multi-hydroxyl functional head groups. Liposomal formulations of these lipids were developed and thoroughly characterized by means of DNA binding ability, size and zeta potential. Optimal lipid-DNA complexes were determined by their transfection efficiency in HEK-293 (Human embryonic kidney) cells. 1,4 gluconic gamma-lactone derived lipid (TS1) and ascorbic acid derived lipid (TS2), have exhibited 25-fold and 12-fold increase in transfected HEPG2 (human liver cancer) cells, respectively, when compared with a control lipid without sugar-like moiety (TA). However, this property was reversed in the case of U87 (human primary glioblastoma) cell line. The results point out that the transfection efficiencies of sugar alcohol-based cationic lipids are cell-dependant. Cytotoxicity of the lipid complexes revealed that the sugar-mimicking cationic lipids are non-toxic as approximate to 80 % viable cells were observed in the treated cell lines. In conclusion, the current paper adds knowledge on the sugar based cationic lipids and reiterates that these lipids could yield potential applications towards liver targeted gene delivery.

Automated summary

These sugar-based cationic lipids show promise as carriers for nucleic acids into cells, with the ability to enhance target oriented uptake and biocompatibility. The study synthesized three new cationic lipid analogues, showing that the transfection efficiency of these lipids is cell-dependent. Additionally, the results demonstrate that sugar-mimicking cationic lipids are non-toxic and hold potential applications for liver targeted gene delivery.