Reduction of Cytotoxicity of Iron Nitride Particles for Magnetic Hyperthermia through Oxidation Treatment

The development of biocompatible magnetic materials is becoming increasingly important alongside advancements in high-performance materials and drug-delivery technologies. Among the candidate materials, iron nitride has attracted interest as a magnetic biomaterial. However, high concentrations of iron nitride have been reported to reduce cell viability because of the leaching of its components. To address this issue, we subjected iron nitride particles, which were synthesized from hematite and sodium amide, to an additional air oxidation treatment to suppress leachate release. In this work, we comprehensively evaluated the material properties and cytotoxicity of the synthesized particles. Material characterization was performed using X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray spectroscopy, and vibrating sample magnetometry, whereas cytotoxicity on L929 murine fibroblasts was assessed through inductively coupled plasma atomic emission spectrometry, pH analysis, and fluorescent staining. This oxidation treatment effectively mitigated pH elevation, decreased the amount of iron ions released, and consequently reduced cytotoxicity by limiting intracellular iron ion uptake. These findings demonstrate that surface oxidation is a promising strategy for mitigating the toxicity of iron nitride. Conversely, the oxidation treatment also diminished the magnetic properties and heat-generation properties under an alternating magnetic field, indicating that further material design is required depending on the intended biomedical application. For the iron nitride particles to be used in biomedical applications, in vivo evaluations using animal models will also be necessary.