Disturbance of ion environment and immune regulation following biodistribution of magnetic iron oxide nanoparticles injected intravenously

Although it is expected that accumulation of metal oxide nanoparticles that can induce redox reaction in the biological system may influence ion homeostasis and immune regulation through generation of free radicals, the relationship is still unclear. In this study, mice received magnetic iron oxide nanoparticles (M-FeNPs, 2 and 4 mg/kg) a single via the tail vein, and their distribution in tissues was investigated over time (1, 4, and 13 weeks). In addition, we evaluated the effects on homeostasis of redox reaction-related elements, the ion environment and immune regulation. The iron level in tissues reached at the maximum on 4 weeks after injection and M-FeNPs the most distributed in the spleen at 13 weeks. Additionally, levels of redox reaction-related elements in tissues were notably altered since 1 week post-injection. While levels of K⁺ and Na⁺ in tissue tended to decrease with time, Ca²⁺ levels reached to the maximum at 4 weeks post-injection. On 13 weeks post-injection, the increased percentages of neutrophils and eosinophils, the enhanced release of LDH, and the elevated secretion of IL-8 and IL-6 were clearly observed in the blood of M-FeNP-treated mice compared to the control. While expression of antigen presentation related-proteins and the maturation of dendritic cells were markedly inhibited following distribution of M-FeNPs, the expression of several chemokines, including CXCR2, CCR5, and CD123, was enhanced on the splenocytes of the treated groups. Taken together, we suggest that accumulation of M-FeNPs may induce adverse health effects by disturbing homeostasis of the immune regulation and ion environment.