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Nanoencapsulation of gla-rich protein (GRP) as a novel approach to target inflammation

2022-05Text Open access
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datacite.subject.fosCiências Médicas
datacite.subject.sdg03:Saúde de Qualidade
dc.contributor.authorViegas, Carla S. B.
dc.contributor.authorAraújo, Nuna
dc.contributor.authorCarreira, Joana
dc.contributor.authorPontes, Jorge F.
dc.contributor.authorMacedo, Anjos L.
dc.contributor.authorVinhas, Maurícia
dc.contributor.authorMoreira, Ana S.
dc.contributor.authorFaria, Tiago Q.
dc.contributor.authorGrenha, Ana
dc.contributor.authorMatos, António A. de
dc.contributor.authorSchurgers, Leon
dc.contributor.authorVermeer, Cees
dc.contributor.authorSimes, Dina C.
dc.date.accessioned2025-11-21T10:31:37Z
dc.date.available2025-11-21T10:31:37Z
dc.date.issued2022-05
dc.description.abstractChronic inflammation is a major driver of chronic inflammatory diseases (CIDs), with a tremendous impact worldwide. Besides its function as a pathological calcification inhibitor, vitamin K-dependent protein Gla-rich protein (GRP) was shown to act as an anti-inflammatory agent independently of its gamma-carboxylation status. Although GRP’s therapeutic potential has been highlighted, its low solubility at physiological pH still constitutes a major challenge for its biomedical application. In this work, we produced fluorescein-labeled chitosan-tripolyphosphate nanoparticles containing non-carboxylated GRP (ucGRP) (FCNG) via ionotropic gelation, increasing its bioavailability, stability, and anti-inflammatory potential. The results indicate the nanosized nature of FCNG with PDI and a zeta potential suitable for biomedical applications. FCNG’s anti-inflammatory activity was studied in macrophage-differentiated THP1 cells, and in primary vascular smooth muscle cells and chondrocytes, inflamed with LPS, TNFα and IL-1β, respectively. In all these in vitro human cell systems, FCNG treatments resulted in increased intra and extracellular GRP levels, and decreased pro-inflammatory responses of target cells, by decreasing pro-inflammatory cytokines and inflammation mediators. These results suggest the retained anti-inflammatory bioactivity of ucGRP in FCNG, strengthening the potential use of ucGRP as an anti-inflammatory agent with a wide spectrum of application, and opening up perspectives for its therapeutic application in CIDs.eng
dc.identifier.citationViegas CSB, Araújo N, Carreira J, Pontes JF, Macedo AL, Vinhas M, Moreira AS, Faria TQ, Grenha A, de Matos AA, et al. Nanoencapsulation of Gla-Rich Protein (GRP) as a Novel Approach to Target Inflammation. International Journal of Molecular Sciences. 2022; 23(9):4813. https://doi.org/10.3390/ijms23094813
dc.identifier.doi10.3390/ijms23094813
dc.identifier.issn1422-0067
dc.identifier.urihttp://hdl.handle.net/10400.26/59924
dc.language.isoeng
dc.peerreviewedyes
dc.publisherMDPI
dc.relation.hasversionhttps://doi.org/10.3390/ijms23094813
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectnanoparticles
dc.subjectGla-rich protein (GRP)
dc.subjectchronic inflammatory diseases (CIDs)
dc.subjectinflammation
dc.subjectvitamin K-dependent protein (VKDP)
dc.titleNanoencapsulation of gla-rich protein (GRP) as a novel approach to target inflammationeng
dc.typetext
dspace.entity.typePublication
oaire.citation.issue9
oaire.citation.startPage4813
oaire.citation.titleInternational Journal of Molecular Sciences
oaire.citation.volume23
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

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