Authors
Ensi Liu, Chang Shen, Qiannan Zhao, Shuai Cheng, Wei Wang, Huicong Feng, Zhen Dai, Zhaoliang Shen, Sen Lin, Xifan Mei
Published in
Small (Weinheim an der Bergstrasse, Germany). Pages e74907. Jul 29, 2026. Epub Jul 29, 2026.
Abstract
Mesenchymal stem cell -derived exosomes (MSCs-EXO) have been increasingly studied due to their high biosafety and excellent drug delivery properties. The use of MSCs-EXO as drug carriers for the treatment of rheumatoid arthritis (RA) has been reported. However, conventional exosomes cannot target the damaged area, significantly reducing their therapeutic efficacy. Therefore, this study proposes a strategy for the rational design of exosomes derived from genetically engineered mesenchymal stem cells, enabling them to target the inflammatory storm in the affected limb, regulate the immune microenvironment, and release similar to superoxide dismutase (SOD-like) and similar to catalase (CAT-like) nanoparticles to eliminate Reactive Oxygen and Nitrogen Species (RONS). RA provides a therapeutic platform for disease repair. MSC transduced with a lentivirus and carrying the anchoring peptide IL-4Rα secrete exosomes containing this peptide (IL-4.EXO), which demonstrates excellent targeting ability. These exosomes encapsulate Prussian blue nanoparticles ([email protected]), forming a synergistic composite exosome delivery system targeting inflammation sites, antioxidant stress, and promoting cartilage joint repair. Micro-CT shows a reduction in cartilage damage. Proteomics confirmed that it inhibits inflammation by affecting the proteasomal pathway through suppression of the PSMD4 protein. This exosome combines regulation of inflammation and antioxidant stress, offering a new therapeutic strategy for RA.
PMID:
42522687
Bibliographic data and abstract were imported from PubMed on 29 Jul 2026.
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