Carbon monoxide (CO)-releasing micelles enable efficient treatment of MRSA-induced septic arthritis and rheumatoid arthritis

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).