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

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.