Sono‐Immunotherapeutic Nanocapturer to Combat Multidrug‐Resistant Bacterial Infections

Antibiotic-free methods hold particular promise for preventing and controlling multidrug-resistant (MDR) bacterial infection via eradiation of bacteria and their pathogenic virulence. A facile and bioinspired strategy is presented for bridging antibacterial sonodynamic therapy and antivirulence immunotherapy. As a proof-of-concept, an antibody which neutralizes alpha-toxin of methicillin-resistant Staphylococcus aureus (MRSA) is genetically engineered on to the surface of cell membrane nanovesicles, which then undergo sonosensitizer encapsulation. Compared with conventional passive virulence absorption using natural red blood membrane, the highly active antibody–toxin interaction enables the nanovesicles to capture virulence more potently in vitro. Upon ultrasound activation, the sonosensitizers efficiently generate reactive oxygen species to kill bacteria and accelerate the virulence clearance. In vivo optical imaging shows that the antibody-piloted nanocapturer can successfully locate MRSA infection and accurately distinguish the foci from sterile inflammation. In situ magnetic resonance imaging and oxyhemoglobin saturation detection visualize the treatment progression, revealing a complete sono-immunotherapeutic eradication of MRSA myositis in mice. The first combination of antibacterial sonodynamic therapy and antivirulence immunotherapy, which promises a new way for antibiotic-free nanotheranostics to robustly combat MDR bacterial infections, is presented.