The metabolic fate of iron-based magnetic nanomaterials and their impact on macrophage function

Iron-based magnetic nanomaterials are increasingly utilized as therapeutic agents because of their unique physicochemical properties. Upon administration, they are predominantly phagocytosed by the mononuclear phagocytic system, where they undergo lysosomal digestion and contribute to cellular iron metabolism, thereby influencing systemic iron homeostasis. Macrophages are the primary targets of iron-based magnetic nanomaterials and they play a crucial role in innate immunity. Functional plasticity and phenotypic alterations are associated with cellular and systemic iron regulation. This review provides a comprehensive discussion of the recent advancements in understanding of the metabolic fate of iron-based nanomaterials within monocytes/macrophages and their impact on macrophage function. The review focuses on investigating the roles of iron-based magnetic nanomaterials in mimicking enzyme-like activities, modulating iron metabolism, influencing cellular signaling pathways, and affecting mitochondrial energy metabolism and magnetic field responsiveness. Furthermore, this review addresses the current strategies and challenges in utilizing iron-based nanomaterials for macrophage-targeted diagnosis and therapy. This review aims to elucidate the complex processes and key factors through which iron-based magnetic nanomaterials mediate macrophage modulation, thereby providing a scientific rationale for the future design of macrophage-targeted applications.