Magnetic Iron Oxide Nanoparticles Enhance Exosome Production by Upregulating Exosome Transport and Secretion Pathways

Exosomes are cell-released nanovesicles that regulate intercellular communication by transporting a variety of bioactive molecules. They play a crucial role in various physiological and pathological processes, such as the immune response, tissue regeneration, aging, and tumor progression. There has been growing interest in controlling exosome production, which could offer valuable tools for unraveling complex cell communication networks and enabling novel therapeutic applications. Magnetic iron oxide nanoparticles (MNPs), one of the few nanomaterials approved for clinical use, have been shown to remotely modulate cellular activities such as cytoskeleton reorganization, ion channel activation, and cell polarization. In this study, we systematically investigate the effects of MNPs, acting as nanoscale force transducers, on exosome production in two distinct cell types with different responses to mechanical stimuli. Our findings reveal that magnetic force applied to intracellular MNPs induces vesicle relocation and promotes the formation of actin stress fibers. Gene expression analysis further shows that intracellular magnetic force upregulates genes related to exosome transport and secretion as well as other pathways linked to exosome biogenesis. Notably, these forces substantially enhance exosome production, particularly MNP-containing exosomes, which are accompanied by increased intercellular exchange of MNPs. In summary, our study offers valuable insights into MNP-driven exosome production and presents potential strategies for enhancing cell communication and modulating nanoparticle distribution in nanomedicine.