Biodegradability of superparamagnetic nanoparticles of iron oxide used as MRI contrast agents in organic tissue and intra-cellular environments

In nanomedecine, ultrasmall superparamagnetic particles of iron oxide (USPIO) are used as MRI contrast agents for variety of applications. However, there is few data available about the biotransformation of USPIOs after their intravenous administration. Metabolic changes include the transformation of USPIO core into ferritin. In this paper, our aim is to present an efficient technique based on magnetic susceptibility measurements and simulations, to reach a statistical determination of both magnetic nanoparticles differentiated by their magnetic size and phase. Indeed, we recently developed an accurate "triple fit" analysis method where the zero-field cooled/field cooled (ZFC/FC) curves and a room temperature magnetization loop are simultaneously adjusted using a semi-analytical model to determine particle magnetic size distribution, moment and anisotropy. Magnetometry measurements have been performed on dehydrated samples of liver and spleen of healthy C57B16 mice after USPIO injection (P904 from Guerbet laboratory) at clinical dose (50 μmol/kg) and sacrifice up to 3 months later. By fitting the entire curves, no appreciable USPIO modification has been detected up to 2 weeks, while continuous magnetic signal degradation is observed from 1 to 2 months with a stabilisation of the number of USPIO which are still present in organs up to 3 months. In parallel, sophisticated HR-TEM and STEM-HAADF experiments allow us to identify the temporal transformation of USPIO into ferritin