Curcumin-modified Mn-based metal–organic framework for synergistic sonodynamic and cascade anti-oxidation therapy of bacterial osteomyelitis

The osteomyelitis induced by methicillin-resistant Staphylococcus aureus (MRSA) remains a formidable clinical challenge due to persistent bacterial infection, chronic inflammation, and impaired bone regeneration. Herein, a multi-functional nanoplatform is prepared by manganese-based porphyrinic metal-organic frameworks (PCN-222(Mn)) modified with curcumin (Cur) for treating bacterial osteomyelitis. The resulting PCN-222(Mn)-Cur nanoparticles exhibit effective sonodynamic antibacterial activity by rapid reactive oxygen species generation, which also has a synergistic effect (antimicrobial rate of 99.98 %) with long-term antibacterial efficiency of curcumin. Besides, the effective cascade anti-oxidation reaction of PCN-222(Mn) can be achieved by superoxide dismutase- and catalase-like activities owing to the MnN 4 active site. In a rat tibial osteomyelitis model, compared with antibiotic therapy, the ultrasound-activated PCN-222(Mn)-Cur platform exhibits superior antibacterial efficacy against MRSA, coupled with synergistic anti-inflammatory effects and promoted osteogenic regeneration capacity. In summary, this biosafe nanoplatform demonstrates excellent bacterial-killing, anti-inflammation, and osteogenesis, offering a prospect for treating refractory bacterial bone infections.