Guanidinium‐Decorated Nanostructure for Precision Sonodynamic‐Catalytic Therapy of MRSA‐Infected Osteomyelitis

Abstract Osteomyelitis caused by methicillin‐resistant Staphylococcus aureus (MRSA) biofilm infection is difficult to eradicate and can even be life‐threatening. Given that the infection is persistent and deep‐seated in the bone tissue, controlled and efficient treatment of osteomyelitis remains challenging. Herein, an activatable nanostructure (Au/TNT@PG) is presented for synergistic sonodynamic‐catalytic therapy of MRSA‐infected osteomyelitis. The Au/TNT@PG backbone is obtained by conjugating a guanidinium‐rich polymer (PG), a component that penetrates the biofilm matrix, onto ultrasound (US)‐absorbing gold‐doped titanate nanotubes (Au/TNTs). Under deep‐penetrating US irradiation, the nanocomposite generates ¹O₂ for sonodynamic therapy and catalyzes the decomposition of endogenous H₂O₂ into toxic •OH in the acidic infection microenvironment for catalytic therapy, leading to bacterial cell death. Its robust antibacterial effectiveness is attributable to its bacteria‐capturing ability, the biofilm penetrability of positively charged guanidinium, and the subsequent synergistic effect of sonodynamic‐catalytic action of Au/TNT. Such a remotely controlled approach potentiates the polarization of macrophages to M2‐type while suppressing the M1‐type, leading to topical inflammation resolution and enhanced osteoblast proliferation and differentiation to inhibit bone loss. Therefore, this study provides a generic nanotherapeutic approach for efficient sonodynamic‐catalytic therapy with respect to osteomyelitis.