An Antibacterial Nanorobotic Approach for the Specific Targeting and Removal of Multiple Drug‐Resistant Staphylococcus aureus

Abstract Methicillin‐resistant Staphylococcus aureus (MRSA) causes diseases ranging from skin infections to lethal sepsis and has become a serious threat to human health due to multiple‐drug resistance (MDR). Therefore, a resistance‐free antibacterial therapy is necessary to overcome MDR MRSA infections. In this study, an antibacterial nanorobot (Ab‐nanobot) is developed wherein a cell wall‐binding domain (CBD)‐endolysin, acting as a sensor, is covalently conjugated with an actuator consisting of an iron oxide/silica core–shell. The CBD‐endolysin sensor shows an excellent specificity to detect, bind, and accumulate on the S. aureus USA300 cell surface even in a bacterial consortium, and in host cell infections. Ab‐nanobot specifically captures and kills MRSA in response to medically approved radiofrequency (RF) electromagnetic stimulation (EMS) signal. When Ab‐nanobot receives the RF‐EMS signal on the cell surface, actuator induces cell death in MRSA with 99.999% removal within 20 min by cell‐wall damage via generation of localized heat and reactive oxygen species. The in vivo efficacy of Ab‐nanobot is proven using a mice subcutaneous skin infection model. Collectively, this study offers a nanomedical resistance‐free strategy to overcome MDR MRSA infections by providing a highly specific nanorobot for S. aureus .