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Treatment with FAP-targeted zinc ferrite nanoparticles for rheumatoid arthritis by inducing endoplasmic reticulum stress and mitochondrial damage
- Source :
- Materials Today Bio, Vol 21, Iss , Pp 100702- (2023)
- Publication Year :
- 2023
- Publisher :
- Elsevier, 2023.
-
Abstract
- Rheumatoid arthritis (RA) is a common chronic inflammatory disease characterized by the proliferation of fibroblast-like synoviocytes (FLS), pannus development, cartilage, and bone degradation, and, eventually, loss of joint function. Fibroblast activating protein (FAP) is a particular product of activated FLS and is highly prevalent in RA-derived fibroblast-like synoviocytes (RA-FLS). In this study, zinc ferrite nanoparticles (ZF-NPs) were engineered to target FAP+ (FAP positive) FLS. ZF-NPswere discovered to better target FAP+ FLS due to the surface alteration of FAP peptide and to enhance RA-FLS apoptosis by activating the endoplasmic reticulum stress (ERS) system via the PERK-ATF4-CHOP, IRE1-XBP1 pathway, and mitochondrial damage of RA-FLS. Treatment with ZF-NPs under the influence of an alternating magnetic field (AMF) can significantly amplify ERS and mitochondrial damage via the magnetocaloric effect. It was also observed in adjuvant-induced arthritis (AIA) mice that FAP-targeted ZF-NPs (FAP-ZF-NPs) could significantly suppress synovitis in vivo, inhibit synovial tissue angiogenesis, protect articular cartilage, and reduce M1 macrophage infiltration in synovium in AIA mice. Furthermore, treatment of AIA mice with FAP-ZF-NPs was found to be more promising in the presence of an AMF. These findings demonstrate the potential utility of FAP-ZF-NPs in the treatment of RA.
Details
- Language :
- English
- ISSN :
- 25900064
- Volume :
- 21
- Issue :
- 100702-
- Database :
- Directory of Open Access Journals
- Journal :
- Materials Today Bio
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.be8800c5408a4aa09909cddf4dc021e7
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.mtbio.2023.100702