Iron oxide nanoparticles oxidize transformed RAW 264.7 macrophages into foam cells: Impact of pulmonary surfactant component dipalmitoylphosphatidylcholine

Abstract

Iron oxide nanoparticles (IONPs) are one of the most important components in airborne particulate matter that originally generated from traffic emission, iron ore mining, coal combustion and melting of engine fragments. Once IONPs entered respiratory tract and deposit in the alveoli, they may interact with pulmonary surfactant (PS) that distributed in the alveolar lining. Thereafter, it is necessary to investigate the interaction of inhaled IONPs and PS, which helps the understanding of health risk of respiratory health induced by IONPs. Using dipalmitoyl phosphatidylcholine (DPPC), the major components of PS, as a lipid model, we explored the interaction of DPPC with typical IONPs, Fe3O4 NPs and amino-functionalized analogue (Fe3O4–NH2 NPs). DPPC was readily adsorbed on the surface of both IONPs. Although DPPC corona depressed the cellular uptake of IONPs, IONPs@DPPC complexes caused higher cytotoxicity toward RAW 264.7 macrophages, compared to pristine IONPs. Mechanistic studies have shown that IONPs react with intracellular hydrogen peroxide, which promotes the Fenton reaction, to generate hydroxyl radicals. Iron ions could oxidize lipids to form lipid peroxides, and lipid hydroperoxides will decompose to generate hydroxyl radicals, which further promote cellular oxidative stress, lipid accumulation, foam cell formation, and the release of inflammatory factors. These findings demonstrated the phenomenon of coronal component oxidation, which contributed to IONPs-induced cytotoxicity. This study offered a brand-new toxicological mechanism of IONPs at the molecular level, which is helpful for further understanding the adverse effects of IONPs.