Nanozyme-driven self-assembled rhein gels for osteoarthritis therapy: Alleviating chondrocyte inflammation by reprogramming macrophages
Osteoarthritis (OA), the fourth leading cause of global disability, is marked by progressive cartilage loss, synovial inflammation, and dysregulated bone remodeling. Current therapeutic strategies are hindered by systemic adverse effects and insufficient intra-articular drug bioavailability, undersc...
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Elsevier
2025-10-01
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| Series: | Materials Today Bio |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006425007318 |
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| author | Jian Jiang Chao Song Xuefeng Hou Kangjie Xu Zhongkai Ji Lei Fan Juqun Xi Ailang Zhang |
| author_facet | Jian Jiang Chao Song Xuefeng Hou Kangjie Xu Zhongkai Ji Lei Fan Juqun Xi Ailang Zhang |
| author_sort | Jian Jiang |
| collection | DOAJ |
| description | Osteoarthritis (OA), the fourth leading cause of global disability, is marked by progressive cartilage loss, synovial inflammation, and dysregulated bone remodeling. Current therapeutic strategies are hindered by systemic adverse effects and insufficient intra-articular drug bioavailability, underscoring the demand for enhanced delivery mechanisms. In this study, we developed a CeO2 nanozyme-driven gel system synergistically integrated with the herbal monomer rhein (RH). The coordinatively unsaturated sites on the CeO2 nanozymes triggered RH self-assembly into a gel through surface coordination interactions. Comprehensive characterization demonstrated that the CeO2/RH gels exhibit synergistic reactive oxygen/nitrogen species (RONS)-scavenging capability, leveraging both the antioxidant enzyme-mimetic activity of CeO2 and the intrinsic properties of RH. The redox-modulatory activity of CeO2/RH gels promoted macrophage polarization from M1 pro-inflammatory to M2 anti-inflammatory phenotypes through phenotypic reprogramming. This immunomodulatory shift substantially reduced inflammatory mediator secretion in macrophages, thereby suppressing chondrocyte apoptosis and senescence through downregulation of the IL-6/JAK2/STAT1 signaling axis via macrophage-chondrocyte crosstalk. In vivo validation using a modified Hulth-induced rat OA model demonstrated the CeO2/RH gels’ therapeutic superiority. Collectively, our findings establish the CeO2/RH gels as a synergistic therapeutic platform for OA intervention, demonstrating dual competency in RONS-scavenging precision and immunomodulatory microenvironment remodeling through redox-biology-mediated cellular cross-talk regulation. |
| format | Article |
| id | doaj-art-16bc1911f8e74a2aad034bea534fe78f |
| institution | Kabale University |
| issn | 2590-0064 |
| language | English |
| publishDate | 2025-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj-art-16bc1911f8e74a2aad034bea534fe78f2025-08-20T03:45:03ZengElsevierMaterials Today Bio2590-00642025-10-013410216110.1016/j.mtbio.2025.102161Nanozyme-driven self-assembled rhein gels for osteoarthritis therapy: Alleviating chondrocyte inflammation by reprogramming macrophagesJian Jiang0Chao Song1Xuefeng Hou2Kangjie Xu3Zhongkai Ji4Lei Fan5Juqun Xi6Ailang Zhang7Clinical Medical Research Center, Binhai County People's Hospital, Binhai Clinical College, Yangzhou University Medical College, Yancheng, Jiangsu, 224000, China; School of Medicine, Institute of Translational Medicine, Yangzhou University, Yangzhou, Jiangsu, 225009, ChinaSchool of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, Jiangsu, 225002, ChinaClinical Medical Research Center, Binhai County People's Hospital, Binhai Clinical College, Yangzhou University Medical College, Yancheng, Jiangsu, 224000, ChinaClinical Medical Research Center, Binhai County People's Hospital, Binhai Clinical College, Yangzhou University Medical College, Yancheng, Jiangsu, 224000, ChinaClinical Medical Research Center, Binhai County People's Hospital, Binhai Clinical College, Yangzhou University Medical College, Yancheng, Jiangsu, 224000, ChinaSchool of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, Jiangsu, 225002, China; Corresponding author.School of Medicine, Institute of Translational Medicine, Yangzhou University, Yangzhou, Jiangsu, 225009, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou, Jiangsu, 225009, China; Corresponding author. School of Medicine, Institute of Translational Medicine, Yangzhou University, Yangzhou, Jiangsu, 225009, China.Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Corresponding author.Osteoarthritis (OA), the fourth leading cause of global disability, is marked by progressive cartilage loss, synovial inflammation, and dysregulated bone remodeling. Current therapeutic strategies are hindered by systemic adverse effects and insufficient intra-articular drug bioavailability, underscoring the demand for enhanced delivery mechanisms. In this study, we developed a CeO2 nanozyme-driven gel system synergistically integrated with the herbal monomer rhein (RH). The coordinatively unsaturated sites on the CeO2 nanozymes triggered RH self-assembly into a gel through surface coordination interactions. Comprehensive characterization demonstrated that the CeO2/RH gels exhibit synergistic reactive oxygen/nitrogen species (RONS)-scavenging capability, leveraging both the antioxidant enzyme-mimetic activity of CeO2 and the intrinsic properties of RH. The redox-modulatory activity of CeO2/RH gels promoted macrophage polarization from M1 pro-inflammatory to M2 anti-inflammatory phenotypes through phenotypic reprogramming. This immunomodulatory shift substantially reduced inflammatory mediator secretion in macrophages, thereby suppressing chondrocyte apoptosis and senescence through downregulation of the IL-6/JAK2/STAT1 signaling axis via macrophage-chondrocyte crosstalk. In vivo validation using a modified Hulth-induced rat OA model demonstrated the CeO2/RH gels’ therapeutic superiority. Collectively, our findings establish the CeO2/RH gels as a synergistic therapeutic platform for OA intervention, demonstrating dual competency in RONS-scavenging precision and immunomodulatory microenvironment remodeling through redox-biology-mediated cellular cross-talk regulation.http://www.sciencedirect.com/science/article/pii/S2590006425007318OsteoarthritisSynovial macrophagesGelEnzyme-mimetic activityAnti-inflammatory |
| spellingShingle | Jian Jiang Chao Song Xuefeng Hou Kangjie Xu Zhongkai Ji Lei Fan Juqun Xi Ailang Zhang Nanozyme-driven self-assembled rhein gels for osteoarthritis therapy: Alleviating chondrocyte inflammation by reprogramming macrophages Materials Today Bio Osteoarthritis Synovial macrophages Gel Enzyme-mimetic activity Anti-inflammatory |
| title | Nanozyme-driven self-assembled rhein gels for osteoarthritis therapy: Alleviating chondrocyte inflammation by reprogramming macrophages |
| title_full | Nanozyme-driven self-assembled rhein gels for osteoarthritis therapy: Alleviating chondrocyte inflammation by reprogramming macrophages |
| title_fullStr | Nanozyme-driven self-assembled rhein gels for osteoarthritis therapy: Alleviating chondrocyte inflammation by reprogramming macrophages |
| title_full_unstemmed | Nanozyme-driven self-assembled rhein gels for osteoarthritis therapy: Alleviating chondrocyte inflammation by reprogramming macrophages |
| title_short | Nanozyme-driven self-assembled rhein gels for osteoarthritis therapy: Alleviating chondrocyte inflammation by reprogramming macrophages |
| title_sort | nanozyme driven self assembled rhein gels for osteoarthritis therapy alleviating chondrocyte inflammation by reprogramming macrophages |
| topic | Osteoarthritis Synovial macrophages Gel Enzyme-mimetic activity Anti-inflammatory |
| url | http://www.sciencedirect.com/science/article/pii/S2590006425007318 |
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