학술논문
Nanoencapsulation of Gla-Rich Protein (GRP) as a Novel Approach to Target Inflammation.
Document Type
Academic Journal
Author
Viegas CSB; Centre of Marine Sciences (CCMAR), Universidade do Algarve, 8005-139 Faro, Portugal.; GenoGla Diagnostics, Centre of Marine Sciences (CCMAR), Universidade do Algarve, 8005-139 Faro, Portugal.; Araújo N; Centre of Marine Sciences (CCMAR), Universidade do Algarve, 8005-139 Faro, Portugal.; Carreira J; Centre of Marine Sciences (CCMAR), Universidade do Algarve, 8005-139 Faro, Portugal.; Pontes JF; Centre of Marine Sciences (CCMAR), Universidade do Algarve, 8005-139 Faro, Portugal.; Macedo AL; UCIBIO-Applied Molecular Biosciences Unit, Departamento de Química, and Associate Laboratory i4HB-Institute for Health and Bioeconomy, NOVA School of Science and Technology, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal.; Vinhas M; Algarve Biomedical Center Research Institute (ABC-RI), Universidade do Algarve, 8005-139 Faro, Portugal.; Moreira AS; iBET-Instituto de Biologia Experimental e Tecnológica, 2780-157 Oeiras, Portugal.; ITQB-Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal.; Faria TQ; iBET-Instituto de Biologia Experimental e Tecnológica, 2780-157 Oeiras, Portugal.; ITQB-Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal.; Grenha A; Centre of Marine Sciences (CCMAR), Universidade do Algarve, 8005-139 Faro, Portugal.; de Matos AA; Centro de Investigação Interdisciplinar Egas Moniz, Egas Moniz-Cooperativa de Ensino Superior CRL, 2829-511 Caparica, Portugal.; Schurgers L; Department of Biochemistry, Cardiovascular Research Institute, Maastricht University, 6229 HX Maastricht, The Netherlands.; Vermeer C; Cardiovscular Research Institute CARIM, Maastricht University, 6229 HX Maastricht, The Netherlands.; Simes DC; Centre of Marine Sciences (CCMAR), Universidade do Algarve, 8005-139 Faro, Portugal.; GenoGla Diagnostics, Centre of Marine Sciences (CCMAR), Universidade do Algarve, 8005-139 Faro, Portugal.
Source
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
Subject
Language
English
Abstract
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 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.