Magnetic field-targeting and ultrasound-responsive antibiotic delivery for enhanced penetration and eradication of bacterial biofilms

Bacteria colonizing medical implants usually lead to biofilm formation and result in persistent infections. Conventional antibiotics often fail to effectively accumulate and penetrate the extracellular polymeric barriers of bacterial biofilms. Thus, there is an urgent need to develop effective antibiotic delivery systems capable of biofilm targeting and disruption. Herein, mesoporous Fe 3 O 4 nanoparticles (mFe NPs) were used to co-load perfluoropentane (PFP) and ciprofloxacin (Cip), constructing magnetic field (MF)/ultrasound (US) dual-responsive mFeP-Cip NPs for eradicating Pseudomonas aeruginosa (PAO1) biofilms on catheter implants. Under magnetic guidance, mFeP-Cip NPs can precisely target PAO1 biofilms. Subsequent US exposure triggers PFP phase transition and vaporization, which disrupts biofilm structure via cavitation effects, thereby enhancing Cip penetration. In a 96-well plate PAO1 biofilm model, the combination of mFeP-Cip NPs with MF/US reduced biofilm biomass and viable bacterial counts by 59 % and 99.9992 %, respectively, while demonstrating efficient biofilm elimination on medical catheters. In a catheter PAO1 infection model in mice, mFeP-Cip NPs achieved a 99.994 % antibacterial efficiency under MF/US stimulation. Additionally, mFeP-Cip NPs exhibited excellent biocompatibility. This work presents an MF/US dual-responsive antibiotic delivery system that synergizes magnetic targeting with US-enhanced antibiotic permeation, offering a promising nanotherapeutic platform for precise and efficient treatment of biofilm-associated infections.