A Non-Viral Plasmid DNA Delivery System Consisting on a Lysine-Derived Cationic Lipid Mixed with a Fusogenic Lipid

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dc.contributor.authorMartínez Negro, María
dc.contributor.authorSánchez Arribas, Natalia
dc.contributor.authorGuerrero Martínez, Andrés
dc.contributor.authorMoyá, María Luisa
dc.contributor.authorTros de Ilarduya, Conchita
dc.contributor.authorMendicuti, Francisco
dc.contributor.authorAicart Sospedra, Emilio
dc.contributor.authorJunquera González, María Elena
dc.date.accessioned2023-06-17T09:09:05Z
dc.date.available2023-06-17T09:09:05Z
dc.date.issued2019-11-27
dc.description.abstractThe insertion of biocompatible amino acid moieties in non-viral gene nanocarriers is an attractive approach that has been recently gaining interest. In this work, a cationic lipid, consisting of a lysine-derived moiety linked to a C12 chain (LYCl) was combined with a common fusogenic helper lipid (DOPE) and evaluated as a potential vehicle to transfect two plasmid DNAs (encoding green fluorescent protein GFP and luciferase) into COS-7 cells. A multidisciplinary approach has been followed: (i) biophysical characterization based on zeta potential, gel electrophoresis, small-angle X-ray scattering (SAXS), and cryo-transmission electronic microscopy (cryo-TEM); (ii) biological studies by fluorescence assisted cell sorting (FACS), luminometry, and cytotoxicity experiments; and (iii) a computational study of the formation of lipid bilayers and their subsequent stabilization with DNA. The results indicate that LYCl/DOPE nanocarriers are capable of compacting the pDNAs and protecting them efficiently against DNase I degradation, by forming Lα lyotropic liquid crystal phases, with an average size of ~200 nm and low polydispersity that facilitate the cellular uptake process. The computational results confirmed that the LYCl/DOPE lipid bilayers are stable and also capable of stabilizing DNA fragments via lipoplex formation, with dimensions consistent with experimental values. The optimum formulations (found at 20% of LYCl content) were able to complete the transfection process efficiently and with high cell viabilities, even improving the outcomes of the positive control Lipo2000*.
dc.description.departmentDepto. de Química Física
dc.description.facultyFac. de Ciencias Químicas
dc.description.refereedTRUE
dc.description.sponsorshipMinisterio de Economía y Competitividad (MINECO)
dc.description.sponsorshipUniversidad Complutense de Madrid
dc.description.sponsorshipUniversidad de Alcalá
dc.description.statuspub
dc.eprint.idhttps://eprints.ucm.es/id/eprint/66770
dc.identifier.doi10.3390/pharmaceutics11120632
dc.identifier.issn1999-4923
dc.identifier.officialurlhttps://doi.org/10.3390/pharmaceutics11120632
dc.identifier.relatedurlhttps://www.mdpi.com/1999-4923/11/12/632
dc.identifier.urihttps://hdl.handle.net/20.500.14352/8281
dc.issue.number12
dc.journal.titlePharmaceutics
dc.language.isoeng
dc.page.initial632
dc.publisherMDPI
dc.relation.projectID(CTQ2015-65972-R, CTQ2015-64425-C2-1-R, CTQ2015-64425-C2-2-R, CTQ2016-80600-P y RTI2018-095844-B-I00)
dc.relation.projectIDUCMA05-33-010
dc.relation.projectIDCCGP2017-EXP/027
dc.rightsAtribución 3.0 España
dc.rights.accessRightsopen access
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/es/
dc.subject.keywordlysine-derived cationic lipid
dc.subject.keywordplasmid DNA
dc.subject.keywordlipoplex
dc.subject.keywordtransfection
dc.subject.keywordprotection
dc.subject.keywordcompaction
dc.subject.keywordgene delivery
dc.subject.keywordmultilamellar aggregates
dc.subject.keywordmolecular dynamics
dc.subject.ucmQuímica física (Física)
dc.subject.ucmQuímica física (Química)
dc.subject.unesco2210 Química Física
dc.titleA Non-Viral Plasmid DNA Delivery System Consisting on a Lysine-Derived Cationic Lipid Mixed with a Fusogenic Lipid
dc.typejournal article
dc.volume.number11
dspace.entity.typePublication
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relation.isAuthorOfPublicationd590ed92-7a5f-481b-abb0-42ad5d4dbd42
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