Abstract
Septic arthritis (SA) and rheumatoid arthritis (RA) are prevalent and challenging joint diseases that often lead to severe consequences, including sepsis, disability, and life-threatening conditions. However, their distinct etiologies and pathological mechanisms require different treatment strategies. We herein report a single formulation of carbon monoxide (CO)-releasing micelles capable of efficient treatment of both SA and RA diseases. Our findings demonstrate that the local release of CO under red light stimulus effectively eradicates methicillin-resistant Staphylococcus aureus (MRSA) pathogens while safeguarding MRSA-infected chondrocytes and osteogenic cells. Furthermore, CO delivery orchestrates macrophage polarization homeostasis via the nuclear factor erythroid-2-related factor (Nrf2)/heme oxygenase-1 (HO-1) pathway, manifesting unique anti-inflammatory and anti-osteoclastic effects. These remarkable properties empower CO-releasing micelles to emerge as a singular treatment approach, addressing both SA and RA in murine models without the need for conventional medications such as antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs).
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