Nanoencapsulation of Gla-Rich Protein (GRP) as a Novel Approach to Target Inflammation
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 g...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-04-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/9/4813 |
| _version_ | 1797504578300674048 |
|---|---|
| author | 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 C. Simes |
| author_facet | 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 C. Simes |
| author_sort | Carla S. B. Viegas |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T04:06:32Z |
| format | Article |
| id | doaj.art-b4acee64e8464c9db7944ec2a7d5c402 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:06:32Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-b4acee64e8464c9db7944ec2a7d5c4022023-11-23T08:22:37ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01239481310.3390/ijms23094813Nanoencapsulation of Gla-Rich Protein (GRP) as a Novel Approach to Target InflammationCarla S. B. Viegas0Nuna Araújo1Joana Carreira2Jorge F. Pontes3Anjos L. Macedo4Maurícia Vinhas5Ana S. Moreira6Tiago Q. Faria7Ana Grenha8António A. de Matos9Leon Schurgers10Cees Vermeer11Dina C. Simes12Centre of Marine Sciences (CCMAR), Universidade do Algarve, 8005-139 Faro, PortugalCentre of Marine Sciences (CCMAR), Universidade do Algarve, 8005-139 Faro, PortugalCentre of Marine Sciences (CCMAR), Universidade do Algarve, 8005-139 Faro, PortugalCentre of Marine Sciences (CCMAR), Universidade do Algarve, 8005-139 Faro, PortugalUCIBIO—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, PortugalAlgarve Biomedical Center Research Institute (ABC-RI), Universidade do Algarve, 8005-139 Faro, PortugaliBET—Instituto de Biologia Experimental e Tecnológica, 2780-157 Oeiras, PortugaliBET—Instituto de Biologia Experimental e Tecnológica, 2780-157 Oeiras, PortugalCentre of Marine Sciences (CCMAR), Universidade do Algarve, 8005-139 Faro, PortugalCentro de Investigação Interdisciplinar Egas Moniz, Egas Moniz-Cooperativa de Ensino Superior CRL, 2829-511 Caparica, PortugalDepartment of Biochemistry, Cardiovascular Research Institute, Maastricht University, 6229 HX Maastricht, The NetherlandsCardiovscular Research Institute CARIM, Maastricht University, 6229 HX Maastricht, The NetherlandsCentre of Marine Sciences (CCMAR), Universidade do Algarve, 8005-139 Faro, PortugalChronic 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.https://www.mdpi.com/1422-0067/23/9/4813nanoparticlesGla-rich protein (GRP)chronic inflammatory diseases (CIDs)inflammationvitamin K-dependent protein (VKDP) |
| spellingShingle | 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 C. Simes Nanoencapsulation of Gla-Rich Protein (GRP) as a Novel Approach to Target Inflammation International Journal of Molecular Sciences nanoparticles Gla-rich protein (GRP) chronic inflammatory diseases (CIDs) inflammation vitamin K-dependent protein (VKDP) |
| title | Nanoencapsulation of Gla-Rich Protein (GRP) as a Novel Approach to Target Inflammation |
| title_full | Nanoencapsulation of Gla-Rich Protein (GRP) as a Novel Approach to Target Inflammation |
| title_fullStr | Nanoencapsulation of Gla-Rich Protein (GRP) as a Novel Approach to Target Inflammation |
| title_full_unstemmed | Nanoencapsulation of Gla-Rich Protein (GRP) as a Novel Approach to Target Inflammation |
| title_short | Nanoencapsulation of Gla-Rich Protein (GRP) as a Novel Approach to Target Inflammation |
| title_sort | nanoencapsulation of gla rich protein grp as a novel approach to target inflammation |
| topic | nanoparticles Gla-rich protein (GRP) chronic inflammatory diseases (CIDs) inflammation vitamin K-dependent protein (VKDP) |
| url | https://www.mdpi.com/1422-0067/23/9/4813 |
| work_keys_str_mv | AT carlasbviegas nanoencapsulationofglarichproteingrpasanovelapproachtotargetinflammation AT nunaaraujo nanoencapsulationofglarichproteingrpasanovelapproachtotargetinflammation AT joanacarreira nanoencapsulationofglarichproteingrpasanovelapproachtotargetinflammation AT jorgefpontes nanoencapsulationofglarichproteingrpasanovelapproachtotargetinflammation AT anjoslmacedo nanoencapsulationofglarichproteingrpasanovelapproachtotargetinflammation AT mauriciavinhas nanoencapsulationofglarichproteingrpasanovelapproachtotargetinflammation AT anasmoreira nanoencapsulationofglarichproteingrpasanovelapproachtotargetinflammation AT tiagoqfaria nanoencapsulationofglarichproteingrpasanovelapproachtotargetinflammation AT anagrenha nanoencapsulationofglarichproteingrpasanovelapproachtotargetinflammation AT antonioadematos nanoencapsulationofglarichproteingrpasanovelapproachtotargetinflammation AT leonschurgers nanoencapsulationofglarichproteingrpasanovelapproachtotargetinflammation AT ceesvermeer nanoencapsulationofglarichproteingrpasanovelapproachtotargetinflammation AT dinacsimes nanoencapsulationofglarichproteingrpasanovelapproachtotargetinflammation |