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 tumorassociated 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