Dicationic Lipophosphoramidates as DNA Carriers

Abstract

Lipophosphoramidates with two different permanent cations as polar heads were synthesized and evaluated for their gene transfer activity. Physicochemical measurements (particle size, zeta potentials) and gel retardation assays were also performed. In vitro biological evaluation was conducted with A542 and HeLa cell lines, and cytotoxicity determined by a chemiluminescent assay. The set of results indicates that, on the whole, dicationic lipophosphoramidates constitute an interesting alternative to their monocationic analogues.

Enhancement of dendritic cells transfection in vivo and of vaccination against B16F10 melanoma with mannosylated histidylated lipopolyplexes loaded with tumor antigen messenger RNA

“…Next, a liposomal formulation comprising three lipids (a mannosylated lipid, an imidazole lipophosphoramidate, and an imidazolium lipophosphoramidate), was added. Lipophosphoramidates have a chemical structure that is bio-inspired from the natural phospholipids present in the cell membranes, and most of these synthetic vectors proved to exhibit a moderate or low toxicity according to in vitro 29,30 and in vivo 31,32 transfection assays. At the best, 11 mol% Man-lipid have been inserted in those liposomes to prepare Man 11 -LPR100.…”

Synthesis and Transfection Activity of New Cationic Phosphoramidate Lipids: High Efficiency of an Imidazolium Derivative

“…These cationic phosphoramidate lipids proved to be efficient in in vitro and in vivo transfection experiments. [13,14,15] In this series of vectors, one of the most efficient (in term of high transfection efficiency and low toxicity) was KLN47 (Scheme 1). These promising results encouraged us to investigate some new structural modifications of phosphoramidate lipids and to evalIn an effort to enhance the gene-transfer efficiencies of cationic lipids and to decrease their toxicities, a series of new phosphoramidate lipids with chemical similarity to cell membrane phospholipids was synthesised.…”

Nature as a source of inspiration for cationic lipid synthesis

“…2). Several structural modifications were performed including variations of the hydrophobic chain length (Le Bolc'h et al 1995;Floch et al 1998), the structure of the linker and of the polar head group Mevel et al 2007). An interesting structural modification was the substitution of the trimethylammonium polar head group by either a trimethylphosphonium or a trimethylarsonium, to decrease the toxicity of the cationic lipids Guenin et al 2000;Picquet et al 2005).…”