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Important role of phosphoramido linkage in imidazole-based dioleyl helper lipids for liposome stability and primary cell transfection

dc.contributor.authorMEVEL, Mathieu
dc.contributor.authorHAUDEBOURG, Thomas
dc.contributor.authorCOLOMBANI, Thibault
dc.contributor.authorPEUZIAT, Pauline
dc.contributor.authorDALLET, Laurence
dc.contributor.authorCHATIN, Benoit
dc.contributor.authorLAMBERT, Olivier
dc.contributor.authorBERCHEL, Mathieu
dc.contributor.authorMONTIER, Tristan
dc.contributor.authorJAFFRES, Paul-Alain
dc.contributor.authorLEHN, Pierre
dc.contributor.authorPITARD, Bruno
dc.date.accessioned2020-09-03T07:56:10Z
dc.date.available2020-09-03T07:56:10Z
dc.date.issued2016
dc.identifier.issn1099-498X
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/10837
dc.description.abstractEnBackground To optimize synthetic gene delivery systems, there is a need to develop more efficient lipid formulations. Most cationic lipid formulations contain 'helper' neutral lipids because of their ability to increase DNA delivery, in particular by improving endosomal escape of DNA molecules via the pH-buffering effect of protonatable groups and/or fusion with the lipid bilayer of endosomes. Methods We evaluated the influence of the linker structure between the two oleyl chains in the helper lipid on transfection efficiency in cell lines, as well as in primary cells (hepatocytes/cardiomyocytes). We reported the synthesis of two new pH-buffering imidazole helper lipids characterized by a polar headgroup containing one (compound 6) or two (compound 5) imidazole groups and two oleyl chains linked by an amide group. We studied their association with the aminoglycoside lipidic derivative dioleylsuccinylparomomycin (DOSP), which contains two oleyl chains linked to the aminoglycoside polar headgroup via an amide function. We compared the morphology and transfection properties of such binary liposomes of DOSP/5 and DOSP/6 with those of liposomes combining DOSP with another imidazole-based dioleyl helper lipid (MM27) in which a phosphoramido group acts as a linker between the two oleyl chains and imidazole function. Results The phosphoramido linker in the helper lipid induces a major difference in terms of morphology and resistance to decomplexation at physical pH for DOSP/helper lipid complexes. Conclusions This hybrid dioleyl linker composition of DOSP/MM27 led to higher transfection efficiency in cell lines and in primary cells compared to complexes with homogeneous dioleyl linker. Copyright (C) 2015 John Wiley & Sons, Ltd.
dc.language.isoen
dc.title.enImportant role of phosphoramido linkage in imidazole-based dioleyl helper lipids for liposome stability and primary cell transfection
dc.typeArticle de revue
dc.subject.halChimie/Matériaux
bordeaux.journalJournal of Gene Medicine
bordeaux.page3-15
bordeaux.volume18
bordeaux.hal.laboratoriesInstitut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN) - UMR 5248*
bordeaux.hal.laboratoriesInstitut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN, UMR 5248)
bordeaux.issue1-3
bordeaux.institutionUniversité de Bordeaux
bordeaux.institutionBordeaux INP
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Journal%20of%20Gene%20Medicine&rft.date=2016&rft.volume=18&rft.issue=1-3&rft.spage=3-15&rft.epage=3-15&rft.eissn=1099-498X&rft.issn=1099-498X&rft.au=MEVEL,%20Mathieu&HAUDEBOURG,%20Thomas&COLOMBANI,%20Thibault&PEUZIAT,%20Pauline&DALLET,%20Laurence&rft.genre=article


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