Mechanism of Iron Oxide-Induced Macrophage Activation: The Impact of Composition and the Underlying Signaling Pathway

Iron oxide nanoparticles (IONPs) have emerging anticancer applications via polarizing tumor-associated macrophages from tumor-promoting phenotype (M2) to tumor-suppressing phenotype (M1). However, the underlying mechanism and structure–function relationship remain unclear. We report magnetite IONPs are more effective compared to hematite in M1 polarization and tumor suppression. Moreover, magnetite IONPs specifically rely on interferon regulatory factor 5 signaling pathway for M1 polarization and down-regulate M2-assoicated arginase-1. This study provides new understandings and paves the way for designing advanced iron-based anticancer technologies.