Sonoactivated Chemodynamic Therapy: A Robust ROS Generation Nanotheranostic Eradicates Multidrug‐Resistant Bacterial Infection

Abstract Although ultrasound‐based therapeutic strategies have achieved great success in the battle against antibiotic‐resistant bacterial infections, various sonodynamic treatments still suffer from poor therapeutic efficiency, failing to completely eradicate infections. Thus, more potent strategies are urgently required. Herein, a novel ultrasound‐driven treatment modality, sonoactivated chemodynamic therapy (SCDT), is proposed, which shows a robust generation of superoxide anion and destructive hydroxyl radical via sonotriggered catalytic reactions. This SCDT platform is prepared by grafting Fe 3+ onto polyethylenimine‐modified bismuth oxybromide (BiOBr) nanoplates. During sonocatalysis, the introduction of Fe 3+ can effectively separate the holes (h + ) and electrons (e ‐ ) of BiOBr NPs and shorten their transport path of valence electrons, resulting in the activation of multioxygen reduction and Fenton reaction to generate abundant reactive oxygen species against methicillin‐resistant Staphylococcus aureus (MRSA) infection. More importantly, Fe 3+ can also serve as a magnetic resonance imaging (MRI) contrast agent to achieve the accurate diagnosis of bacterial infection. The SCDT‐mediated bactericidal outcome can be monitored by in situ monitoring through MRI technique, revealing a complete elimination of MRSA myositis in mice. Collectively, its deep tissue penetration, high therapeutic efficacy, and noninvasive properties make SCDT a promising therapeutic modality for combating multidrug‐resistant bacterial infection.