Interface/Dipole Polarized Antibiotics‐Loaded Fe₃O₄/PB Nanoparticles for Non‐Invasive Therapy of Osteomyelitis Under Medical Microwave Irradiation

Abstract Due to their poor light penetration, photothermal therapy and photodynamic therapy are ineffective in treating deep tissue infections, such as osteomyelitis caused by Staphylococcus aureus (S. aureus). Here, a microwave (MW)‐responsive magnetic targeting composite system consisting of ferric oxide (Fe₃O₄)/Prussian blue (PB) nanoparticles, gentamicin (Gent), and biodegradable poly(lactic‐co‐glycolic acid) (PLGA) is reported. The PLGA/Fe₃O₄/PB/Gent complex is used in combination with MW thermal therapy (MTT), MW dynamic therapy (MDT), and chemotherapy (CT) to treat acute osteomyelitis infected with S. aureus‐infected. The powerful antibacterial effect of the PLGA/Fe₃O₄/PB/Gent is determined by the synergistic effects of heat and reactive oxygen species (ROS) generation by the Fe₃O₄/PB nanoparticles under MW irradiation and the effective release of Gent at the infection site via magnetic targeting. The antibacterial mechanism of the PLGA/Fe₃O₄/PB/Gent under MW irradiation is analyzed using bacterial transcriptome RNA sequencing. The MW heat and ROS reduce the activity of the protein transporters on the bacterial membrane, along with the transport of various ions and the acceleration of phosphate metabolism, which can lead to increased permeability of the bacterial membrane, damage the ribosome and DNA, and accompany the internal protein efflux of the bacteria, thus effectively killing the bacteria.