From degradation to (re)magnetization: magnetic reprogramming of maghemite (Massart), magnetite, cobalt ferrite and ferrihydrite nanoparticles by human stem cells

Abstract

Iron-based nanostructures, whether environmental or synthetic, can infiltrate the human body and interact with cells due to their nanoscale dimensions. Some human cells, upon the internalization of iron oxide nanoparticles and their biodegradation, are capable of de novo biosynthesis of magnetic nanostructures. This process is evidenced by a transient loss and subsequent recovery of magnetic signal, a phenomenon termed "cellular re-magnetization". In this study, we explored the intracellular fate of four types of iron-based nanoparticles: maghemite (Massart), magnetite, cobalt ferrite, and ferrihydrite. They were internalized by human mesenchymal stem cells that were then cultured under both biodegradation and biosynthesis conditions. Transmission electron microscopy revealed structural modifications of all four nanoparticle types over time, indicating active processing by the cells. Under biodegradation conditions, the cells exhibited a progressive decrease in magnetic signal from day 0 to 21. In contrast, under biosynthesis conditions, magnetometry showed a drop in magnetic signal from day 0 to day 3/9 for maghemite, magnetite, and cobalt ferrite, followed by a signal recovery at day 9/21, consistent with the de novo biosynthesis of superparamagnetic structures. For ferrihydrite, initially paramagnetic, a weak superparamagnetic signal emerged on day 21 in cells under biosynthesis conditions. These results support the efficiency of the in vitro cell model, where cells internalize and degrade exogenous nanoparticles and reroute released iron to generate biogenic magnetic nanostructures.