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Lauroylated histidine-enriched S4(13)-PV peptide as an efficient gene silencing mediator in cancer cells

dc.contributor.authorMorais, Catarina M.
dc.contributor.authorCardoso, Ana M.
dc.contributor.authorAguiar, Luisa
dc.contributor.authorVale, Nuno
dc.contributor.authorNóbrega, Clévio
dc.contributor.authorZuzarte, Monica
dc.contributor.authorGomes, Paula
dc.contributor.authorPedroso de Lima, Maria C.
dc.contributor.authorJurado, Amalia S.
dc.date.accessioned2021-06-24T11:35:17Z
dc.date.available2021-06-24T11:35:17Z
dc.date.issued2020-09-04
dc.description.abstractPurposeThis study aimed to endow the cell-penetrating peptide (CPP) S4(13)-PV with adequate features towards a safe and effective application in cancer gene therapy.MethodsPeptide/siRNA complexes were prepared with two new derivatives of the CPP S4(13)-PV, which combine a lauroyl group attached to the N- or C-terminus with a histidine-enrichment in the N-terminus of the S4(13)-PV peptide, being named C12-H-5-S4(13)-PV and H-5-S4(13)-PV-C12, respectively. Physicochemical characterization of siRNA complexes was performed and their cytotoxicity and efficiency to mediate siRNA delivery and gene silencing in cancer cells were assessed in the absence and presence of serum.ResultsPeptide/siRNA complexes prepared with the C12-H-5-S4(13)-PV derivative showed a nanoscale (ca. 100 nm) particle size, as revealed by TEM, and efficiently mediated gene silencing (37%) in human U87 glioblastoma cells in the presence of 30% serum. In addition, the new C12-H-5-S4(13)-PV-based siRNA delivery system efficiently downregulated stearoyl-CoA desaturase-1, a key-enzyme of lipid metabolism overexpressed in cancer, which resulted in a significant decrease in the viability of U87 cells. Importantly, these complexes were able to spare healthy human astrocytes.ConclusionsThese encouraging results pave the way for a potential application of the C12-H-5-S4(13)-PV peptide as a promising tool in cancer gene therapy.
dc.description.sponsorshipEuropean Regional Development Fund (ERDF), through the Centro 2020 Regional Operational Programme [CENTRO-010145-FEDER-000008]
dc.description.sponsorshipEuropean Regional Development Fund (ERDF), through the COMPETE 2020 -Operational Programme for Competitiveness and Internationalisation
dc.description.sponsorshipPortuguese national funds via FCT - Fundacao para a Ciencia e a Tecnologia [POCI-01-0145-FEDER-016390: CANCEL STEM, POCI-01-0145-FEDER-007440, UIDB/04539/2020]
dc.description.sponsorshipFundacao para a Ciencia e Tecnologia (FCT, Portugal)Portuguese Foundation for Science and Technology [UID/QUI/50006/2013, UID/MULTI/04378/2013, IF/00092/2014, SFRH/BD/79077/2011, PD/BD/106035/2015]
dc.description.versioninfo:eu-repo/semantics/publishedVersion
dc.identifier.doi10.1007/s11095-020-02904-x
dc.identifier.issn0724-8741
dc.identifier.urihttp://hdl.handle.net/10400.1/16396
dc.language.isoeng
dc.peerreviewedyes
dc.publisherSpringer
dc.subjectCancer
dc.subjectCell-penetrating peptide
dc.subjectCell viability
dc.subjectGene silencing
dc.subjectStearoyl-CoA desaturase-1
dc.subject.otherChemistry
dc.titleLauroylated histidine-enriched S4(13)-PV peptide as an efficient gene silencing mediator in cancer cells
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue10
oaire.citation.startPage188
oaire.citation.titlePharmaceutical Research
oaire.citation.volume37
person.familyNameNóbrega
person.givenNameClévio
person.identifier.ciencia-idC510-7F41-BAF8
person.identifier.orcid0000-0002-8312-5292
person.identifier.ridM-6047-2013
person.identifier.scopus-author-id24473454000
rcaap.rightsrestrictedAccess
rcaap.typearticle
relation.isAuthorOfPublication725ea6f8-1363-4cee-9cf2-5ac7303b3ba9
relation.isAuthorOfPublication.latestForDiscovery725ea6f8-1363-4cee-9cf2-5ac7303b3ba9

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