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The use of a selective, nontoxic dual-acting peptide for breast cancer patients with brain metastasis

2024Journal article Open access
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dc.contributor.authorCavaco, Marco
dc.contributor.authorPérez-Peinado, Clara
dc.contributor.authorValle, Javier
dc.contributor.authorSilva, Rúben
dc.contributor.authorGano, Lurdes
dc.contributor.authorCorreia, João D. G.
dc.contributor.authorAndreu, David
dc.contributor.authorCastanho, Miguel A. R. B.
dc.contributor.authorNeves, Vera
dc.date.accessioned2024-05-02T13:31:59Z
dc.date.available2024-05-02T13:31:59Z
dc.date.issued2024
dc.description© 2024 The Authors. Published by Elsevier Masson SAS. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/).pt_PT
dc.description.abstractTriple-negative breast cancer (TNBC) is an aggressive subtype characterized by the absence of commonly targeted receptors. Unspecific chemotherapy is currently the main therapeutic option, with poor results. Another major challenge is the frequent appearance of brain metastasis (BM) associated with a significant decrease in patient overall survival. The treatment of BM is even more challenging due to the presence of the blood-brain barrier (BBB). Here, we present a dual-acting peptide (PepH3-vCPP2319) designed to tackle TNBC/BM, in which a TNBC-specific anticancer peptide (ACP) motif (vCPP2319) is joined to a BBB peptide shuttle (BBBpS) motif (PepH3). PepH3-vCPP2319 demonstrated selectivity and efficiency in eliminating TNBC both in monolayers (IC50≈5.0 µM) and in spheroids (IC50≈25.0 µM), with no stringent toxicity toward noncancerous cell lines and red blood cells (RBCs). PepH3-vCPP2319 was also able to cross the BBB in vitro and penetrate the brain in vivo, and was stable in serum with a half-life above 120 min. Tumor cell-peptide interaction is fast, with quick peptide internalization via clathrin-mediated endocytosis without membrane disruption. Upon internalization, the peptide is detected in the nucleus and the cytoplasm, indicating a multi-targeted mechanism of action that ultimately induces irreversible cell damage and apoptosis. In conclusion, we have designed a dual-acting peptide capable of brain penetration and TNBC cell elimination, thus expanding the drug arsenal to fight this BC subtype and its BM.pt_PT
dc.description.sponsorshipThe project leading to these results have received funding from 'la Caixa' Foundation (ID 100010434) and FCT, I.P under the agreement LCF/PR/HP21/52310015; and “Fundação para a Ciência e Tecnologia” (FCT, Portugal) (grant: PD/BD/128281/2017, PTDC/BTM-MAT/2472/2021, UIDB/04349/2020, PTDC/QUI-OUT/3854/2021, and 2021.00895.CEECIND). Work at UPF Department of Medicine and Life Sciences (MELIS) also supported by MCIN “María de Maeztu” Program for Units of Excellence in R&D (CEX2018–000792-M).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationBiomed Pharmacother. 2024 May:174:116573pt_PT
dc.identifier.doi10.1016/j.biopha.2024.116573pt_PT
dc.identifier.eissn1950-6007
dc.identifier.issn0753-3322
dc.identifier.urihttp://hdl.handle.net/10451/64637
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationLCF/PR/HP21/52310015pt_PT
dc.relationPD/BD/128281/2017pt_PT
dc.relationPTDC/BTM-MAT/2472/2021pt_PT
dc.relationUIDB/04349/2020pt_PT
dc.relationPTDC/QUI-OUT/3854/2021pt_PT
dc.relation2021.00895.CEECINDpt_PT
dc.relationCEX2018–000792-Mpt_PT
dc.relation.publisherversionhttps://www.sciencedirect.com/journal/biomedicine-and-pharmacotherapypt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.subjectAnticancer peptidespt_PT
dc.subjectBBB peptide shuttlept_PT
dc.subjectBlood-brain barrierpt_PT
dc.subjectBrain metastasispt_PT
dc.subjectCell-penetrating peptidespt_PT
dc.subjectPepH3pt_PT
dc.subjectTriple-negative breast cancerpt_PT
dc.subjectvCPP2319pt_PT
dc.titleThe use of a selective, nontoxic dual-acting peptide for breast cancer patients with brain metastasispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.titleBiomedicine & Pharmacotherapypt_PT
oaire.citation.volume174pt_PT
person.familyNameCavaco
person.familyNameSilva
person.familyNameBarrela Patricio Gano
person.familyNameCorreia
person.familyNameCastanho
person.familyNameNeves
person.givenNameMarco
person.givenNameRúben
person.givenNameMaria Lurdes
person.givenNameJoão
person.givenNameMiguel
person.givenNameVera
person.identifier1069324
person.identifierJ-6929-2013
person.identifier1064683
person.identifier953259
person.identifier.ciencia-id1412-63B8-7494
person.identifier.ciencia-id561A-878D-536F
person.identifier.ciencia-idC11F-51E3-6084
person.identifier.ciencia-idEC11-F3E9-78A2
person.identifier.ciencia-id671C-1860-A160
person.identifier.orcid0000-0002-0938-9038
person.identifier.orcid0000-0003-3665-9571
person.identifier.orcid0000-0001-7186-2060
person.identifier.orcid0000-0002-7847-4906
person.identifier.orcid0000-0001-7891-7562
person.identifier.orcid0000-0002-2989-7208
person.identifier.ridJ-7036-2013
person.identifier.ridO-2176-2018
person.identifier.scopus-author-id8976995900
person.identifier.scopus-author-id7202364104
person.identifier.scopus-author-id56605575600
person.identifier.scopus-author-id26537945300
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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relation.isAuthorOfPublication.latestForDiscoveryce7bbed1-4210-464f-93ac-f270ca7d2140

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