Abstract
Iron oxide nanoparticles (IONPs) have been increasingly used in various biomedical applications in preclinical and clinical settings. Although the interactions of IONPs with macrophages have been well-reported in the context of nanoparticle toxicity, harnessing the capacity of IONPs in reprograming macrophages towards bactericidal activity has not been explored. Here, using an in vitro culture model of macrophages and an in vivo mouse model of skin wound infection by Staphylococcus aureus (S. aureus), we demonstrated that IONPs in combination with a strategy to trigger the Fenton reaction could significantly enhance bactericidal effects of macrophages against intracellular S. aureus by inducing a M1 macrophage polarization that stimulates the production of reactive oxygen species. Our study supports that harnessing the characteristic of IONPs to tune macrophage polarization to exhibit a bactericidal activity may provide a new strategy for treating infectious diseases.