Ji Penghao, Qiu Shuwen, Huang Junchao, Wang Liping, Wang Yuemei, Wu Peng, Huo Minfeng, Shi Jianlin
Department of Orthopedics, Shanghai Tenth People's Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, The Institute for Biomedical Engineering & Nano Science School of Medicine, School of Medicine, Tongji University, Shanghai, 200072, P. R. China.
State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics Chinese Academy of Sciences, Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences (2021RU012), Shanghai, 200050, P. R. China.
Adv Mater. 2025 Feb;37(7):e2415543. doi: 10.1002/adma.202415543. Epub 2024 Dec 26.
Rheumatoid arthritis (RA) is a kind of inflammation homeostasis disorder that dysfunctions the joints. Clinically, medications against RA focus simply on mitigating the focal inflammation, without considering pro-osteogenesis re-modeling of the bone microenvironment. In the present work, 2D layered calcium disilicide nanoparticles (CSNs) are fabricated by facile aqueous exfoliation. The hydrolysis of CSNs produces anti-oxidative H, alkaline Ca(OH), and silica. These moieties play significant roles in anti-oxidation, anti-inflammation, and pro-osteogenesis resulting in considerably better RA therapeutic consequences than anti-inflammation alone. Hydrogen gas is validated to eliminate excessive hydroxyl radicals and regulate macrophage re-polarization; the generated Ca(OH) can neutralize the acidic microenvironment and inhibit the osteoclast activity; and, the dissolved Ca can effectively complex with phosphates to mineralize Ca(PO), promoting the osteogenesis of the focal joint. The multifunctional performances of CSNs are further confirmed in arthritic mouse and rabbit models, providing an advanced and robust therapeutic strategy against RA with high biocompatibility and clinical transformable promises.
类风湿性关节炎（RA）是一种导致关节功能障碍的炎症稳态紊乱疾病。临床上，治疗RA的药物仅专注于减轻局部炎症，而未考虑骨微环境的促骨生成重塑。在本研究中，通过简便的水相剥离法制备了二维层状二硅化钙纳米颗粒（CSNs）。CSNs的水解产生抗氧化性的H、碱性Ca(OH)₂和二氧化硅。这些成分在抗氧化、抗炎和促骨生成方面发挥着重要作用，从而产生比单独抗炎更好的RA治疗效果。已证实氢气可消除过量的羟基自由基并调节巨噬细胞重极化；生成的Ca(OH)₂可中和酸性微环境并抑制破骨细胞活性；并且，溶解的Ca²⁺可与磷酸盐有效络合以矿化Ca₃(PO₄)₂，促进局部关节的骨生成。CSNs的多功能性能在关节炎小鼠和兔模型中得到进一步证实，为RA提供了一种具有高生物相容性和临床转化前景的先进且有效的治疗策略。
