Magnetic Field/Ultrasound-Responsive FeO Microbubbles for Targeted Mechanical/Catalytic Removal of Bacterial Biofilms.

Conventional antibiotics are limited by drug resistance, poor penetration, and inadequate targeting in the treatment of bacterial biofilm-associated infections. Microbubble-based ultrasound (US)-responsive drug delivery systems can disrupt biofilm structures and enhance antibiotic penetration through cavitation effects. However, currently developed US-responsive microbubbles still depend on antibiotics and lack targeting capability. In this work, magnetic field/ultrasound (MF/US)-responsive FeO microbubbles (FMB) were constructed based on FeO nanoparticles (NPs) with superparamagnetic and peroxidase-like catalytic properties. In vitro experiments demonstrated that FMB can be targeted to methicillin-resistant Staphylococcus aureus (MRSA) biofilms by the direction of MF. Upon US irradiation, FMB collapse due to inertial cavitation and generate mechanical forces to disrupt the structure of MRSA biofilms and releases FeO NPs, which catalyze the generation of reactive oxygen species (ROS) from HO in the biofilm microenvironment and kill the bacteria within the biofilm. In a mouse biofilm infection model, FMB efficiently destroyed MRSA biofilms grown in subcutaneous catheters with the MF and US. Magnetic-targeted mechanical/catalytic therapy based on FMB provides a promising strategy for effectively combating bacterial biofilm infection.