Journal
ORGANIC & BIOMOLECULAR CHEMISTRY
Volume 9, Issue 7, Pages 2422-2432Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c0ob00981d
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- Association Francaise contre les Myopathies (Evry, France)
- Association de Transfusion Sanguine et de Biogenetique Gaetan Saleun (Brest, France)
- Conseil Regional de Bretagne
- Brest Metropole Oceane
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The synthesis of cationic lipo-thiophosphoramidates, a new family of cationic lipids designed for gene delivery, is reported herein. This new class of lipids is less polar than its oxygenated equivalent the lipo-phosphoramidates. Fluorescence anisotropy and FRET were used to determine the fluidity and fusogenicity of the lipo-phosphoramidates 3a-b and lipo-thiophosphoramidates 7a-b. The determination of both the size and the zeta potential of the nano-objects (liposomes and lipoplexes) and the determination of the DNA binding ability of the liposomes have completed the physico-chemical characterizations of the cationic lipids studied. Finally, the cationic lipids 3a-b and 7a-c have been evaluated as synthetic vectors for gene transfection into a variety of mammalian cell lines. The lipo-thiophosphoramidate 7a proved to be an efficient and low toxicity synthetic vector even when used at low lipid to DNA charge ratios.
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