Long term fate of iron oxide nanoparticles in the body: a long and comprehensive survey

Florence Gazeau

MSC Université Paris Diderot/CNRS, USPC, Paris, France

Iron oxide nanoparticles (IONPs) are among the most promising nanomaterials in biomedicine mostly due to their unique magnetic properties but also to their biocompatibility and degradability. However, some questions remain on their long-term fate and biotransformation in the organism. How long will the nanoparticles keep their magnetic properties and be useful for applications? Where does the degradation take place? What are the mechanisms? What is the fate of degradation products? Is there any recycling and transfer between organs? What is the journey of the different particle components, the core and the shell? Which biological response/adaptation to IONP overload and degradation?

I will present some of our latest results regarding the fate of different types of IONP in mice. A part of my talk will focus on a possible pathway for metabolizing IONP degradation products through a protein involved in iron metabolism, the ferritin. We have studied, in solution, the degradation processes of iron oxide nanoparticles in the presence of ferritin proteins as well as the iron transfer processes from nanoparticles to ferritin. The difficulty is the high concentration of endogenous iron which makes it impossible to demonstrate such transfers in vivo. Thus, we have developed a strategy to track these phenomena in vivo by doping iron oxide nanoparticles with a scarce element in the organism, such as cobalt. This work highlighted a possible mechanism of biological recycling, remediation and detoxification of metal oxide nanoparticles mediated by endogenous proteins at the molecular scale. We also developed a multi-scale method to study the life cycle of iron oxide nanoparticles and their by-products in the organism. The main challenge is to differentiate iron steming from the nanoparticles from endogeneous iron. This specific tracking problem is routinely encountered in geochemical studies and solved by labelling the target material with minor stable isotopes. Therefore, iron oxide nanoparticles enriched in the minor stable isotope 57Fe were synthetised and injected intravenously in mice to follow dynamic circulations of iron oxide nanoparticles and their by-products over a period of six months. We have also labelled the particle coating to track the integrity of nanoparticles over time and decipher the specific fates of inorganic core and organic shell. Results of this comprehensive in vivo study will be discussed together with modifications of gene expression related to the presence, accumulation and degradation of IONPs at different doses and in different organs. Comparison with different types of materials, e.g. gold nanoparticles, will be highlighted.