title: "HFP" fluorinated cationic lipids for enhanced lipoplex stability and gene delivery.
abstract: Although a great number of cationic lipids have been designed and evaluated as gene delivery systems, there is still a need for improvement of nonviral vectors. Recently, cationic lipids incorporating terminal fluoroalkyl segments ("FHP" lipids) have been described to display remarkable transfection potency. Here, we describe the synthesis of a new family of fluorinated triblock cationic lipids in which a fluorous segment lays between the cationic and the lipophilic parts of the molecule ("HFP" lipids). The compounds were designed so their self-assembly would offer enhanced resistance toward the host's degradation mechanisms mediated by lipophilic insertion. Self-assembly properties of these cationic lipids were evaluated at the air-water interface where they collapse in a highly ordered liquid phase. The HFP lipids efficiently condense DNA, and the resulting lipoplexes display enhanced resistance to amphiphilic agents when compared to nonfluorinated or FHP cationic lipids. Transfection properties of the fluorinated vectors, alone or as mixtures with different helper lipids (DOPE and a fluorinated analogue of DOPE), were then investigated on different cell lines (BHK-21, HepG2, and HeLa) and compared to those of the reference cationic lipid DOTAP. Data show that impermeabilization of the lipidic phase by fluorous segments alter significantly the gene transfection activities. Remarkably, incorporation of DOPE within the lipoplexes provides the particles with high gene transfection activity without reducing their resistance to amphiphilic agents.
authors.affiliation: Laboratoire de Conception et Application de Molecules Bioactives, CNRS-Universite de Strasbourg, 74 route du Rhin, BP 60024, 67401 Illkirch Cedex, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Klein
authors.forename: Miahala
authors.initials: M
authors.lastname: Ciobanu
authors.forename: Jérôme
authors.initials: J
authors.lastname: Klein
authors.forename: Valérie
authors.initials: V
authors.lastname: Machi
authors.forename: Christian
authors.initials: C
authors.lastname: Leborgne
authors.forename: Thierry
authors.initials: T
authors.lastname: Vandamme
authors.forename: Benoît
authors.initials: B
authors.lastname: Frisch
authors.forename: Françoise
authors.initials: F
authors.lastname: Pons
authors.forename: Antoine
authors.initials: A
authors.lastname: Kichler
authors.forename: Guy
authors.initials: G
authors.lastname: Zuber
authors.forename: Luc
authors.initials: L
authors.lastname: Lebeau
mesh_terms: D000473:Alkanes / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D015195:Drug Design; D004355:Drug Stability; D054879:Halogenation; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000138:chemical synthesis / Q000737:chemistry*; D014162:Transfection / Q000379:methods*
chemical_list: D000473:Alkanes; D008055:Lipids; D004247:DNA