Injectable Glycosaminoglycan Hydrogel with Immunosuppressive Exosomes for Macrophage Polarization and Cartilage Repair in a Rheumatoid Arthritis Treatment.
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| Titel: | Injectable Glycosaminoglycan Hydrogel with Immunosuppressive Exosomes for Macrophage Polarization and Cartilage Repair in a Rheumatoid Arthritis Treatment. |
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| Autoren: | Zhang J; Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China., Huang X; Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China., Wu X; Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China., Zhu L; Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China., Hu J; Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China., Xu X; Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China., Shen Q; Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China., Xu X; Shulan International Medical College, Zhejiang Shuren University, Hangzhou 310015, China., Teng C; Department of Orthopedic Surgery, The Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu 32200, China., Du Y; Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.; Jinhua Institute of Zhejiang University, Jinhua, Zhejiang 321299, China. |
| Quelle: | ACS applied materials & interfaces [ACS Appl Mater Interfaces] 2025 Nov 12; Vol. 17 (45), pp. 61784-61798. Date of Electronic Publication: 2025 Oct 31. |
| Publikationsart: | Journal Article |
| Sprache: | English |
| Info zur Zeitschrift: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 101504991 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1944-8252 (Electronic) Linking ISSN: 19448244 NLM ISO Abbreviation: ACS Appl Mater Interfaces Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Washington, D.C. : American Chemical Society |
| MeSH-Schlagworte: | Exosomes*/chemistry , Arthritis, Rheumatoid*/drug therapy , Arthritis, Rheumatoid*/pathology , Hydrogels*/chemistry , Hydrogels*/pharmacology , Glycosaminoglycans*/chemistry , Glycosaminoglycans*/pharmacology , Immunosuppressive Agents*/chemistry , Immunosuppressive Agents*/pharmacology, Animals ; Rats ; Macrophages/drug effects ; Methotrexate/chemistry ; Methotrexate/pharmacology ; Methotrexate/therapeutic use ; Cartilage/drug effects ; Mice ; Humans ; Arthritis, Experimental/drug therapy ; Arthritis, Experimental/pathology ; Rats, Sprague-Dawley ; Male ; Hyaluronic Acid/chemistry |
| Abstract: | Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and dysfunction. Although existing treatments can alleviate symptoms, they lack a comprehensive and effective approach for treating RA. Exosomes have gained widespread attention as excellent drug delivery carriers with therapeutic potential. Tumor-derived exosomes, owing to their immunosuppressive properties, hold promise for immune regulation and may positively impact the treatment of RA. This study presents a delivery system using a cartilage matrix hyaluronic acid-chondroitin sulfate hydrogel (HC hydrogel) loaded with methotrexate-loaded osteosarcoma-derived exosomes (Exo@MTX). The injectable self-healing HC hydrogel, along with the exosomes, enables sustained release of MTX via local injection, reducing the frequency of administration and minimizing side effects. Furthermore, the system components work synergistically, not only providing immune regulation and anti-inflammatory effects by scavenging reactive oxygen species (ROS) and modulating macrophage M2 polarization but also protecting chondrocytes and promoting joint cartilage repair. Overall, this system integrates anti-inflammatory, immunoregulatory, and cartilage repair effects, demonstrating excellent therapeutic efficacy in a collagen-induced arthritis (CIA) rat model. It offers a potential therapeutic strategy leveraging tumor-derived exosome-mediated immunosuppressive effects, presenting a significant stride in RA treatment strategies. |
| Contributed Indexing: | Keywords: combined therapy; immunosuppressive exosomes; injectable hydrogel; macrophage polarization; rheumatoid arthritis |
| Substance Nomenclature: | 0 (Hydrogels) YL5FZ2Y5U1 (Methotrexate) 0 (Glycosaminoglycans) 0 (Immunosuppressive Agents) 9004-61-9 (Hyaluronic Acid) |
| Entry Date(s): | Date Created: 20251031 Date Completed: 20251113 Latest Revision: 20251113 |
| Update Code: | 20251114 |
| DOI: | 10.1021/acsami.5c16825 |
| PMID: | 41170676 |
| Datenbank: | MEDLINE |
Nájsť tento článok vo Web of Science | Abstract: | Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and dysfunction. Although existing treatments can alleviate symptoms, they lack a comprehensive and effective approach for treating RA. Exosomes have gained widespread attention as excellent drug delivery carriers with therapeutic potential. Tumor-derived exosomes, owing to their immunosuppressive properties, hold promise for immune regulation and may positively impact the treatment of RA. This study presents a delivery system using a cartilage matrix hyaluronic acid-chondroitin sulfate hydrogel (HC hydrogel) loaded with methotrexate-loaded osteosarcoma-derived exosomes (Exo@MTX). The injectable self-healing HC hydrogel, along with the exosomes, enables sustained release of MTX via local injection, reducing the frequency of administration and minimizing side effects. Furthermore, the system components work synergistically, not only providing immune regulation and anti-inflammatory effects by scavenging reactive oxygen species (ROS) and modulating macrophage M2 polarization but also protecting chondrocytes and promoting joint cartilage repair. Overall, this system integrates anti-inflammatory, immunoregulatory, and cartilage repair effects, demonstrating excellent therapeutic efficacy in a collagen-induced arthritis (CIA) rat model. It offers a potential therapeutic strategy leveraging tumor-derived exosome-mediated immunosuppressive effects, presenting a significant stride in RA treatment strategies. |
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| ISSN: | 1944-8252 |
| DOI: | 10.1021/acsami.5c16825 |