Author(s):
Viegas, Carla S. B. ; Araújo, Nuna ; Carreira, Joana ; Pontes, Jorge F. ; Macedo, Anjos L. ; Vinhas, Maurícia ; Moreira, Ana S. ; Faria, Tiago Q. ; Grenha, Ana ; de Matos, António A. ; Schurgers, Leon ; Vermeer, Cees ; Simes, Dina Costa
Date: 2022
Persistent ID: http://hdl.handle.net/10362/143302
Origin: Repositório Institucional da UNL
Project/scholarship:
info:eu-repo/grantAgreement/FCT/3599-PPCDT/EXPL%2FBTM-TEC%2F0990%2F2021/PT;
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04326%2F2020/PT;
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04326%2F2020/PT;
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04378%2F2020/PT;
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04378%2F2020/PT;
info:eu-repo/grantAgreement/FCT/OE/PD%2FBD%2F137064%2F2018/PT;
Subject(s): chronic inflammatory diseases (CIDs); Gla-rich protein (GRP); inflammation; nanoparticles; vitamin K-dependent protein (VKDP); Catalysis; Molecular Biology; Spectroscopy; Computer Science Applications; Physical and Theoretical Chemistry; Organic Chemistry; Inorganic Chemistry; SDG 3 - Good Health and Well-being
Description
LA/P/0101/2020 LA/P/0140/2020 AAC nº 41/ALG/2020—Project nº 072583—NUTRISAFE
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.
