title: Fine tuning of mixed ionic and hydrogen bond interactions for plasmid delivery using lipoplexes.
abstract: Non viral gene transfection has been mostly reached via cationic polymer and lipid, required for DNA complexation and cell internalisation. However, cationic charges often induce cytotoxicity and limit the efficacy of the lipoplexes in vivo due to their fast elimination from the blood stream. Few years ago, we had developed noncationic lipid interacting with DNA via hydrogen bond interactions. To take advantage of both the internalisation efficacy of cationic complexes and the higher DNA release efficacy of non cationic lipids, we chose to mix both ionic and hydrogen bond interactions within one lipoplex. The idea behind this strategy would be to reduce the overall charge while maintaining a high level of transfection. Four mixed formulations of cationic lipid and thiourea lipid were prepared. We found that decreasing ionic interactions and increasing hydrogen bond interactions improved cationic lipoplexes properties. Indeed, we showed that replacement of net positive charges by hydrogen bond interactions with DNA phosphates led to efficient lipoplexes for in vitro DNA transfection at lower cationic charge content, which consequently reduced lipoplex cytotoxicity.
authors.affiliation: Paris Sorbonne Cité, Paris Descartes University, Faculty of Pharmacy, Team Vectors for Targeted Therapy and Molecular Imaging, CNRS UMR 8258, INSERM U1022, 75270 Paris Cedex 06, France.
authors.forename: Johanne
authors.initials: J
authors.lastname: Seguin
authors.affiliation: Paris Sorbonne Cité, Paris Descartes University, Faculty of Pharmacy, Team Vectors for Targeted Therapy and Molecular Imaging, CNRS UMR 8258, INSERM U1022, 75270 Paris Cedex 06, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Dhotel
authors.affiliation: Cell and Molecular Imaging Platform, CRP2 - UMS 3612 CNRS - US25 Inserm-IRD - Université Paris Descartes Paris Sorbonne Cité, Faculty of Pharmacy, 75270 Paris Cedex 06, France.
authors.forename: René
authors.initials: R
authors.lastname: Kai-Luen
authors.affiliation: Paris Sorbonne Cité, Paris Descartes University, Faculty of Pharmacy, Team Vectors for Targeted Therapy and Molecular Imaging, CNRS UMR 8258, INSERM U1022, 75270 Paris Cedex 06, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Bessodes
authors.affiliation: Paris Sorbonne Cité, Paris Descartes University, Faculty of Pharmacy, Team Vectors for Targeted Therapy and Molecular Imaging, CNRS UMR 8258, INSERM U1022, 75270 Paris Cedex 06, France. Electronic address: Nathalie.Mignet@parisdescartes.fr.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Mignet
mesh_terms: D000818:Animals; D002412:Cations / Q000737:chemistry*; D045744:Cell Line, Tumor; D004247:DNA / Q000008:administration & dosage*; D018014:Gene Transfer Techniques; D006860:Hydrogen Bonding; D007477:Ions / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D051379:Mice; D010957:Plasmids / Q000008:administration & dosage*; D014162:Transfection / Q000379:methods
chemical_list: D002412:Cations; D007477:Ions; D008055:Lipids; D008081:Liposomes; D004247:DNA
keywords: Cationic lipids; DNA delivery; Lipoplexes; Nanomedicine; Thiourea lipids; Transfection