Inflammation-Targeting Fullerene Nanoparticles Dually Inhibit Macrophage and Osteoclast Differentiation for Mitigating Rheumatoid Arthritis

In rheumatoid arthritis (RA), the presence of substantial inflammatory macrophages and osteoclasts in joints is known to contribute to the progression of articular inflammation and bone destruction. Herein, we develop a sialic acid -modified tetra malonic acid derivative of C70 fullerene (STMF). STMF possesses inflammation -targeting capability that can effectively impede the differentiation of macrophages and osteoclasts, offering a potential treatment strategy for RA. STMF acts as a mimic of sialyl Lewis x, enabling it to specifically bind with E-selectin, which is overexpressed on inflamed endothelial cells. This selective binding results in a targeted distribution of STMF to inflamed joints, addressing articular inflammation. Upon uptake by macrophages, STMF demonstrates the ability to effectively eliminate intracellular reactive oxygen species and deactivate the downstream events, thereby suppressing their differentiation into M1 -phenotype and osteoclastogenesis. In our experiments using collagen -induced arthritis mouse models, STMF significantly improves paw swelling and redness, mitigates articular inflammation with reduced M1 macrophages, lessens osteoclasts, and repairs bone erosion with neglectable side effects. These findings suggest that STMF has potential as a therapeutic agent for RA, leveraging inflammation -targeting fullerene nanomaterials.