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

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). [Display omitted] •PCO can release CO under red light irradiation, demonstrating robust antibacterial activity against MRSA.•Localized CO delivery shifts macrophages from pro-inflammatory (M1) to anti-inflammatory phenotype (M2).•PCO can serve as a singular therapeutic approach in treatingseptic arthritis and rheumatoid arthritis in a rodent model.