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

Lihui Yuwen,Yuan Liu,Fengjiao Xu,Chi Zhang,Xiaolong Chen,Zhaowei Yin,Bin Liang,Lianhui Wang

Bacterial biofilms are difficult to treat with traditional antibiotics. Ultrasound (US)-responsive antibacterial agents have emerged as promising alternatives for the treatment of bacterial biofilm infections. However, they often suffer from antibiotic dependence, lack of targeting, and low antibacterial efficiency. Herein, we develop Fe3O4/MnCO3 microbubbles (FMMB) by self-assembly of Fe3O4 nanoparticles (Fe3O4 NPs) and MnCO3 nanoparticles (MnCO3 NPs). By the direction of magnetic field (MF), FMMB can be targeted to the Staphylococcus aureus (MRSA) biofilm. Under US irradiation, FMMB can destroy the structure of MRSA biofilms by cavitation-induced mechanical effects and kill bacteria by MnCO3 NPs generated reactive oxygen species (ROS) through the sonodynamic effect. In the mice model with catheter MRSA biofilm infection, FMMB removed 70.4% of the biofilm with MF and US, and the bacteria inactivation efficiency reached as high as 99.999% (4.9 Log). This work develops multifunctional microbubbles with both US-responsive mechanical and sonodynamic effects for biofilm destruction and MF-responsive properties for biofilm targeting, which provides a promising strategy for the design of antibiofilm agents to effectively treat bacterial biofilm infections.