Potential Application of a Water-Soluble Fullerene C60 Decorated with Diethylene Glycol in Treatment of Osteoarthritis

Inflammatory macrophages play a role in cartilage degeneration associated with osteoarthritis (OA) via signaling cascades that result in production of inflammatory substances. This study aims to characterize compound F2, C₆₀(NCH₂CH₂OCH₂CH₂OH)₅, a newly synthesized ethoxyethanol derivative of iminofullerene, and its potential to reduce inflammatory macrophage activity. First, compound F2 is synthesized and labeled with ^99mTc to create ^99mTc-F2. It is then added to lipopolysaccharide (LPS)-exposed bone marrow macrophages (BMMs) to determine its effect on macrophage activation, nitric oxide production, and expression of inflammatory markers iNOS, IL-6, Fpr2, and TLR4. An animal model of osteoarthritis is also injected with ^99mTc-F2 to visualize its localization in vivo. This study demonstrates successful synthesis and radiolabeling of the compound F2 molecule. It also demonstrates that compound F2 reduces nitrite production and suppresses the expression of TNF α, IL-6, iNOS, Fpr2, and TLR4 in BMMs exposed to LPS. Additionally, in rats with surgically transected anterior cruciate ligaments, intravenous administration of radioisotope-labeled compound F2 exhibits selective enrichment in the injured knee. These findings suggest that compound F2 mitigates macrophage activation, decreases inflammatory marker expression, and is located to damaged areas, highlighting its potential as a therapeutic option for OA management.