Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/93834
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dc.contributor.authorFonseca, Nuno A.-
dc.contributor.authorGregório, Ana C.-
dc.contributor.authorMendes, Vera M.-
dc.contributor.authorLopes, Rui-
dc.contributor.authorAbreu, Teresa-
dc.contributor.authorGonçalves, Nélio-
dc.contributor.authorManadas, Bruno-
dc.contributor.authorLacerda, Manuela-
dc.contributor.authorFigueiredo, Paulo-
dc.contributor.authorPereira, Marta-
dc.contributor.authorGaspar, Manuela-
dc.contributor.authorColelli, Fabiana-
dc.contributor.authorPesce, Daniela-
dc.contributor.authorSignorino, Giacomo-
dc.contributor.authorFocareta, Laura-
dc.contributor.authorFucci, Alessandra-
dc.contributor.authorCardile, Francesco-
dc.contributor.authorPisano, Claudio-
dc.contributor.authorCruz, Tony-
dc.contributor.authorAlmeida, Luís-
dc.contributor.authorMoura, Vera-
dc.contributor.authorSimões, Sérgio-
dc.contributor.authorMoreira, João N.-
dc.date.accessioned2021-03-23T15:12:53Z-
dc.date.available2021-03-23T15:12:53Z-
dc.date.issued2021-04-
dc.identifier.issn17480132pt
dc.identifier.urihttp://hdl.handle.net/10316/93834-
dc.description.abstractPatients with breast or ovarian cancer have not benefited from improved efficacy with pegylated liposomal doxorubicin relative to free drug, likely due to the limited extent of the enhanced permeability and retention (EPR) effect, further compromising drug bioavailability in the tumor. Herein it is hypothesized that targeting nucleolin overexpressed in tumor endothelial cells (readily accessible from the vascular compartment), besides cancer cells, with PEGASEMP (doxorubicin hydrochloride in a lipid-based pegylated nanoparticle functionalized with a 31-aminoacid peptide targeting nucleolin), lessens the dependence on high systemic exposures and EPR effect for successful tumor targeting. This strategy has resulted in improved intracellular tumor bioavailability of doxorubicin, at low systemic exposure, associated with a safe toxicological profile. Levels of cell surface nucleolin dictated the antitumor activity of PEGASEMP against nucleolin-overexpressing solid tumors of diverse histological origin, evidencing a significant growth inhibition of malignant mesothelioma over the standard of care. Those observations were paralleled by an impairment of the nucleolin-positive vasculature and downregulation of typically overexpressed genes. Patient stratification based on nucleolin mRNA expression correlated with prognosis and enabled identification of breast and mesothelioma tumors that may potentially benefit from PEGASEMP. Overall, a novel principle of drug delivery is presented with potential therapeutic impact across nucleolin-overexpressing human cancers.pt
dc.language.isoengpt
dc.publisherElsevierpt
dc.relationPOCI-01-0145-FEDER-016390 (acronym: CANCEL STEM)pt
dc.relationHealthy Aging 2020: CENTRO-01-0145-FEDER-000012pt
dc.relationinfo:eu-repo/grantAgreement/EC/FP7/234811/EU/EUROpean network of trans-national collaborative RTD in the field of NANOMEDicinept
dc.rightsembargoedAccesspt
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt
dc.subjectNucleolinpt
dc.subjectTargeted-drug deliverypt
dc.subjectMesotheliomapt
dc.subjectBreast cancerpt
dc.subjectNucleolin-overexpressing cancerspt
dc.titleGMP-grade nanoparticle targeted to nucleolin downregulates tumor molecular signature, blocking growth and invasion, at low systemic exposurept
dc.typearticle-
degois.publication.firstPage101095pt
degois.publication.titleNano Todaypt
dc.relation.publisherversionhttps://www.sciencedirect.com/science/article/pii/S1748013221000207#keys0005pt
dc.peerreviewedyespt
dc.identifier.doi10.1016/j.nantod.2021.101095pt
degois.publication.volume37pt
dc.date.embargo2023-04-01*
uc.date.periodoEmbargo730pt
item.languageiso639-1en-
item.fulltextCom Texto completo-
item.grantfulltextembargo_20230401-
crisitem.author.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.author.orcid0000-0001-5820-9964-
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais
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This item is licensed under a Creative Commons License Creative Commons