Nanoencapsulation of Gla-Rich Protein (GRP) as a Novel Approach to Target Inflammation

Carla S. B. Viegas, Nuna Araújo, Joana Carreira, Jorge F. Pontes, Anjos L. Macedo, Maurícia Vinhas, Ana S. Moreira, Tiago Q. Faria, Ana Grenha, António A. de Matos, Leon Schurgers, Cees Vermeer, Dina Costa Simes

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3 Citations (Scopus)
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Chronic 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 bioavail-ability, 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.

Original languageEnglish
Article number4813
Number of pages18
JournalInternational Journal of Molecular Sciences
Issue number9
Publication statusPublished - 27 Apr 2022


  • chronic inflammatory diseases (CIDs)
  • Gla-rich protein (GRP)
  • inflammation
  • nanoparticles
  • vitamin K-dependent protein (VKDP)


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