Massive Intracellular Biodegradation of Iron Oxide Nanoparticles Evidenced Magnetically at Single-Endosome and Tissue Levels.

Quantitative studies of the long-term fate of iron oxide nanoparticles inside cells, a prerequisite for regenerative medicine applications, are hampered by the lack of suitable biological tissue models and analytical methods. Here, we propose stem-cell spheroids as a tissue model to track intracellular magnetic nanoparticle transformations during long-term tissue maturation. We show that global spheroid magnetism can serve as a fingerprint of the degradation process, and we evidence a near-complete nanoparticle degradation over a month of tissue maturation, as confirmed by electron microscopy. Remarkably, the same massive degradation was measured at the endosome level by single-endosome nanomagnetophoretic tracking in cell-free endosomal extract. Interestingly, this spectacular nanoparticle breakdown barely affected iron homeostasis: only the genes coding for ferritin light chain (iron loading) and ferroportin (iron export) were up-regulated 2-fold by the degradation process. Besides, the magnetic and tis...