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Probing the in vitro mechanism of action of cationic lipid/DNA lipoplexes at a nanometric scale

hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorLE BIHAN, Olivier
hal.structure.identifierITX - unité de recherche de l'institut du thorax [ITX]
dc.contributor.authorCHÈVRE, Raphaël
hal.structure.identifierInstitut de Chimie de la Matière Condensée de Bordeaux [ICMCB]
dc.contributor.authorMORNET, Stéphane
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorGARNIER, Boris
hal.structure.identifierIn Cell Art
hal.structure.identifierITX - unité de recherche de l'institut du thorax [ITX]
dc.contributor.authorPITARD, Bruno
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorLAMBERT, Olivier
dc.date.issued2011
dc.identifier.issn0305-1048
dc.description.abstractEnCationic lipids are used for delivering nucleic acids (lipoplexes) into cells for both therapeutic and biological applications. A better understanding of the identified key-steps, including endocytosis, endosomal escape and nuclear delivery is required for further developments to improve their efficacy. Here, we developed a labelling protocol using aminated nanoparticles as markers for plasmid DNA to examine the intracellular route of lipoplexes in cell lines using transmission electron microscopy. Morphological changes of lipoplexes, membrane reorganizations and endosomal membrane ruptures were observed allowing the understanding of the lipoplex mechanism until the endosomal escape mediated by cationic lipids. The study carried out on two cationic lipids, bis(guanidinium)-tris(2-aminoethyl)amine-cholesterol (BGTC) and dioleyl succinyl paramomycin (DOSP), showed two pathways of endosomal escape that could explain their different transfection efficiencies. For BGTC, a partial or complete dissociation of DNA from cationic lipids occurred before endosomal escape while for DOSP, lipoplexes remained visible within ruptured vesicles suggesting a more direct pathway for DNA release and endosome escape. In addition, the formation of new multilamellar lipid assemblies was noted, which could result from the interaction between cationic lipids and cellular compounds. These results provide new insights into DNA transfer pathways and possible implications of cationic lipids in lipid metabolism.
dc.language.isoen
dc.publisherOxford University Press
dc.rights.urihttp://creativecommons.org/licenses/by-nc/
dc.title.enProbing the in vitro mechanism of action of cationic lipid/DNA lipoplexes at a nanometric scale
dc.typeArticle de revue
dc.identifier.doi10.1093/nar/gkq921
dc.subject.halChimie/Matériaux
bordeaux.journalNucleic Acids Research
bordeaux.page1595-1609
bordeaux.volume39
bordeaux.issue4
bordeaux.peerReviewedoui
hal.identifierhal-00566862
hal.version1
hal.popularnon
hal.audienceInternationale
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-00566862v1
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