Gemini Cationic Lipid-Type Nanovectors Suitable for the Transfection of Therapeutic Plasmid DNA Encoding for Pro-Inflammatory Cytokine Interleukin-12

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dc.contributor.authorSánchez Arribas, Natalia
dc.contributor.authorMartínez Negro, María
dc.contributor.authorAicart Ramos, Clara
dc.contributor.authorTros de Ilarduya, Conchita
dc.contributor.authorAicart Sospedra, Emilio
dc.contributor.authorGuerrero Martínez, Andrés
dc.contributor.authorJunquera González, Elena
dc.date.accessioned2023-06-17T08:25:31Z
dc.date.available2023-06-17T08:25:31Z
dc.date.issued2021-05-15
dc.description.abstractAmple evidence exists on the role of interleukin-12 (IL-12) in the response against many pathogens, as well as on its remarkable antitumor properties. However, the unexpected toxicity and disappointing results in some clinical trials are prompting the design of new strategies and/or vectors for IL-12 delivery. This study was conceived to further endorse the use of gemini cationic lipids (GCLs) in combination with zwitterionic helper lipid DOPE (1,2-dioleoyl-sn-glycero-3-phosphatidyl ethanol amine) as nanovectors for the insertion of plasmid DNA encoding for IL-12 (pCMV-IL12) into cells. Optimal GCL formulations previously reported by us were selected for IL-12-based biophysical experiments. In vitro studies demonstrated efficient pCMV-IL12 transfection by GCLs with comparable or superior cytokine levels than those obtained with commercial control Lipofectamine2000*. Furthermore, the nanovectors did not present significant toxicity, showing high cell viability values. The proteins adsorbed on the nanovector surface were found to be mostly lipoproteins and serum albumin, which are both beneficial to increase the blood circulation time. These outstanding results are accompanied by an initial physicochemical characterization to confirm DNA compaction and protection by the lipid mixture. Although further studies would be necessary, the present GCLs exhibit promising characteristics as candidates for pCMV-IL12 transfection in future in vivo applications.
dc.description.departmentDepto. de Química Física
dc.description.facultyFac. de Ciencias Químicas
dc.description.refereedTRUE
dc.description.sponsorshipMinisterio de Ciencia e Innovación (MICINN)
dc.description.sponsorshipComunidad de Madrid
dc.description.sponsorshipInsituto de Salud Carlos III (ISCIII)/FEDER
dc.description.sponsorshipUniversidad Complutense de Madrid
dc.description.statuspub
dc.eprint.idhttps://eprints.ucm.es/id/eprint/71786
dc.identifier.doi10.3390/pharmaceutics13050729
dc.identifier.issn1999-4923
dc.identifier.officialurlhttps://doi.org/10.3390/pharmaceutics13050729
dc.identifier.urihttps://hdl.handle.net/20.500.14352/7068
dc.issue.number5
dc.journal.titlePharmaceutics
dc.language.isoeng
dc.page.initial729
dc.publisherMDPI
dc.relation.projectID(RTI2018-095844-B-I00 and RTI2018-097609-B-C22)
dc.relation.projectIDNANOBIOCARGO-CM (P2018/NMT-4389)
dc.relation.projectIDPT17/0019
dc.relation.projectID(UCMA05-33-010, GR2019/2020-910447 and GR29/20)
dc.rightsAtribución 3.0 España
dc.rights.accessRightsopen access
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/es/
dc.subject.cdu544
dc.subject.keywordNon-viral gene delivery
dc.subject.keywordGemini cationic lipid
dc.subject.keywordTransfection
dc.subject.keywordProtein corona
dc.subject.keywordInterleukin-12
dc.subject.keywordPro-inflammatory cytokine
dc.subject.ucmQuímica física (Química)
dc.titleGemini Cationic Lipid-Type Nanovectors Suitable for the Transfection of Therapeutic Plasmid DNA Encoding for Pro-Inflammatory Cytokine Interleukin-12
dc.typejournal article
dc.volume.number13
dspace.entity.typePublication
relation.isAuthorOfPublicationd590ed92-7a5f-481b-abb0-42ad5d4dbd42
relation.isAuthorOfPublicationb21e6658-9ad1-4fed-bbf1-e41299c40c84
relation.isAuthorOfPublication56e24a94-c784-43f3-8f0b-19917deee155
relation.isAuthorOfPublication22761001-a3ad-4b9e-b47f-bfd3ba5f8a57
relation.isAuthorOfPublication.latestForDiscoveryd590ed92-7a5f-481b-abb0-42ad5d4dbd42
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