Transfection with Fluorinated Lipoplexes Based on New Fluorinated Cationic Lipids and in the Presence of a Bile Salt Surfactant

详细信息    查看全文

• 作者：Caroline Boulanger ; Christophe Di Giorgio ; Jé ; rô ; me Gaucheron ; and Pierre Vierling
• 刊名：Bioconjugate Chemistry
• 出版年：2004
• 出版时间：July 2004
• 年：2004
• 卷：15
• 期：4
• 页码：901 - 908
• 全文大小：117K
• 年卷期：v.15,no.4(July 2004)
• ISSN：1520-4812

文摘

The synthesis of two fluorinated cationic lipids, which are analogues of frequently used syntheticgene carrier agents (including the cationic 2,3-dioleoyloxy-N-[2-(spermine-carboxamido)ethyl]-N,N-dimethyl-1-propanaminium (DOSPA) component of the commercially available liposomal Lipofectamine), and the disintegration and DNA accessibility (evaluated by the ethidium bromide (BET)intercalation assay) as well as the in vitro transfection efficacy of cationic lipoplexes formulated withthese new lipids in conjunction with conventional or fluorinated helper lipids, in the absence or presenceof sodium taurocholate (STC), a powerful anionic bile salt detergent, is reported. A higher stability,with respect to the STC lytic activity and DNA accessibility, of the fluorinated cationic lipoplexes ascompared with their respective lipofectamine-based ones was demonstrated. Indeed, while theLipofectamine lipoplexes were fully disintegrated at a [STC]/[lipid] molar ratio of 2000, only 40-60%of the DNA intercalation sites of the lipoplexes based on the fluorinated analogue of DOSPA wereaccessible to ethidium bromide. A higher transfection potential in the presence of STC was furtherfound for the lipoplexes formulated with the fluorinated analogue of DOSPA as compared with theLipofectamine preparation. For a STC concentration of 7.5 mM, lipofection mediated with thesefluorinated lipoplexes was significantly higher (nearly 30- to 50-fold, p < 0.05) than with theLipofectamine ones. These results confirm the remarkable transfection potential of fluorinatedlipoplexes.