期刊
ADVANCED MATERIALS
卷 34, 期 30, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.202202715
关键词
denfensomes; mitochondrial dysfunction; mitochondrial targeting; nanoenzymes; osteoarthritis; synovial macrophages
类别
资金
- Key Program of NSFC [81730067]
- Major Project of NSFC [81991514]
- Jiangsu Provincial Key Medical Center Foundation
- Jiangsu Provincial Medical Outstanding Talent Foundation
- Jiangsu Provincial Medical Youth Talent Foundation
- Jiangsu Provincial Key Medical Talent Foundation
- Fundamental Research Funds for the Central Universities [14380493, 14380494]
- National Science Foundation of China [82002370, 31800806, 82000069]
- China Postdoctoral Science Foundation [2019M661806]
- Natural science foundation of Jiangsu province [BK20200117, BK20200314]
- Jiangsu postdoctoral research support project [2021K059A]
- Program of Innovation and Entrepreneurship of Jiangsu Province
In this study, the authors developed a method to reprogram the metabolic function of M1 synovial macrophages using camouflaged meta-Defensomes. The results showed that these nanoparticles successfully transformed the macrophages into the anti-inflammatory M2 phenotype, leading to the suppression of osteoarthritis progression. This study provides a novel approach for the treatment and inhibition of osteoarthritis.
Osteoarthritis (OA) is a low-grade inflammatory and progressive joint disease, and its progression is closely associated with an imbalance in M1/M2 synovial macrophages. Repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype is emerging as a strategy to alleviate OA progression but is compromised by unsatisfactory efficiency. In this study, the reprogramming of mitochondrial dysfunction is pioneered with a camouflaged meta-Defensome, which can transform M1 synovial macrophages into the M2 phenotype with a high efficiency of 82.3%. The meta-Defensome recognizes activated macrophages via receptor-ligand interactions and accumulates in the mitochondria through electrostatic attractions. These meta-Defensomes are macrophage-membrane-coated polymeric nanoparticles decorated with dual ligands and co-loaded with S-methylisothiourea and MnO2. Meta-Defensomes are demonstrated to successfully reprogram the mitochondrial metabolism of M1 macrophages by scavenging mitochondrial reactive oxygen species and inhibiting mitochondrial NO synthase, thereby increasing mitochondrial transcription factor A expression and restoring aerobic respiration. Furthermore, meta-Defensomes are intravenously injected into collagenase-induced osteoarthritis mice and effectively suppress synovial inflammation and progression of early OA, as evident from the Osteoarthritis Research Society International score. Therefore, reprogramming the mitochondrial metabolism can serve as a novel and practical approach to repolarize M1 synovial macrophages. The camouflaged meta-Defensomes are a promising therapeutic agent for impeding OA progression in tclinic.
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