Fe₃O₄/MnCO₃ microbubbles for efficient elimination of bacterial biofilms by mechanical/sonodynamic effects under ultrasound irradiation and magnetic field targeting

Bacterial biofilms present significant challenges in treatment with traditional antibiotics. Ultrasound (US)-responsive antibacterial agents have emerged as promising alternatives for treating bacterial biofilm infections. However, these agents are often limited by antibiotic dependence, inadequate targeting, and low antibacterial efficacy. Herein, we develop Fe₃O₄/MnCO₃ microbubbles (FMMB) by self-assembly of Fe₃O₄ nanoparticles (Fe₃O₄ NPs) and MnCO₃ nanoparticles (MnCO₃ NPs). Under the direction of the magnetic field (MF), FMMB can be directed toward the methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) biofilm. Under US irradiation, FMMB can disrupt the structure of MRSA biofilms by cavitation-induced mechanical effects and kill bacteria with reactive oxygen species (ROS) generated by MnCO₃ NPs through the sonodynamic effect. In a mouse model with catheter-associated MRSA biofilm infection, FMMB removed 58.8% of the biofilm with MF and US, and the bacterial inactivation efficiency reached as high as 4.1 log (99.992%). This work develops multifunctional microbubbles with both US-responsive mechanical and sonodynamic effects for biofilm disruption and MF-responsive properties for biofilm targeting, offering a promising strategy for designing antibiofilm agents to effectively treat bacterial biofilm infections.