Biotransformation of iron oxide nanoparticles and their impact on biokinetics in rats after the intratracheal instillation

Abstract

Understanding the biokinetics of inhaled nanomaterials is essential for evaluating their potential adverse effects, yet current analytical methods may not account for biotransformation—where nanoparticles are transformed into new particle types. This study compared the biokinetics of partially soluble Fe₂O₃ and poorly soluble TiO₂ to investigate how biotransformation influences lung clearance kinetics. Test nanoparticles (140 µg/rat) were instilled into the lungs of rats, and quantitative and qualitative assessments were performed on samples collected from the lungs on days 0, 1, 7, 14, 28, and 90 post-instillation. Notably, this study focused on the biokinetics of particulate forms within the lungs to specifically address particokinetics. Fe₂O₃ exhibited biphasic clearance kinetics, with rapid clearance in the early phase (days 0 to 14; half-life of 13 days) and slow clearance in the late phase (days 14 to 90; half-life 123 days). This biphasic pattern was attributed to the erosion of Fe₂O₃ into smaller, nanometer-sized particles, approximately 40% of which persisted in the lungs for over 3 months. These retained particles showed reduced oxidative potential and were sequestered in ferritin protein, mitigating potential toxicity. In contrast, TiO₂ exhibited a monophasic clearance pattern with a half-life of 88 days and did not exhibit particle degradation. These findings underscore the critical role of biotransformation in understanding the long-term safety and toxicity of inhaled nanomaterials, highlighting the need for comprehensive studies to assess their biological fate and potential risks. Further research should focus on potential adverse effects due to particle overload, interactions with biomolecules, and disruptions in metal homeostasis.