Brain Accumulation of Airborne Magnetite Nanoparticles under Earphone/Smartphone-Embedded Magnetic Fields Triggers Neurotoxicity

Magnetism is an important property of nanomaterials. Natural, incidental, and engineered magnetic nanoparticles are ubiquitous in nature and human activities. As an air pollutant, magnetite nanoparticles (MNPs) can enter the human body and even the brain, posing serious health concerns. However, unlike other physicochemical properties such as size, shape, or surface chemistry, the influence of magnetism on nanoparticle biodistribution and toxicity remains unclear. The manifestation of nanoparticle magnetism requires exposure to magnetic fields, which are ubiquitous in daily life, such as those from mobile phones and earphones. Here, we used six-to eight-week-old C57BL/6J mice coexposed to airborne MNPs and earphone/smartphone-embedded magnetism (EEM) to investigate the impact of nanomaterial magnetism on the <i>in vivo</i> fate and neurotoxicity of inhaled nanoparticles. Co-exposure significantly impaired cognitive performance, as evidenced by reduced target quadrant entries and increased escape latency in the Morris water maze (<i>p</i> < 0.01). EEM increased brain accumulation of inhaled MNPs by approximately 5-fold compared to non-EEM controls. Transcriptomics, immunohistochemistry, metallomics, and reactome profiling, revealed neurodegeneration-related molecular alterations enriched in the Mitogen-Activated Protein Kinase (MAPK) and guanosine triphosphatase-associated signaling pathways. Compared to exposure to non-EEM, or nonmagnetic engineered iron oxide nanoparticles or magnetism-reduced fine particulate matter (PM_2.5), the magnetism-mediated toxicity mechanism induced more severe behavioral damage in mice. Our findings reveal the link between nanomaterial magnetism and toxicity, discovering that exogenous nanoparticles can act as a direct medium <i>in vivo</i> for the health impacts of magnetic field exposure, and provide novel insights into the health impacts of magnetic field exposure and air pollution.