The role of cell-released microvesicles in the intercellular transfer of magnetic nanoparticles in the monocyte/macrophage system

Mononuclear phagocyte system is the first target for injected nanomaterials. Monocytes/macrophages are the central actors for trafficking and clearance of magnetic nanoparticles in vivo. However the fate of nanosized magnetic label is an ongoing issue. Here we demonstrate that the monocyte/macrophage system shows a complex dynamic behavior with respect to iron-oxide nanoparticles uptake. Once internalized by monocytes or macrophages, magnetic nanoparticles can be released by cells upon stress or activation. We identified membrane vesicles shed by activated or apoptotic cells as the carriers transporting magnetic nanomaterials. These vesicles are taken up by naïve macrophages and trigger an intercellular transfer of the magnetic label. They also lead to the redistribution of magnetic label during differentiation of magnetically-labeled monocytes into macrophages. Intercellular transfer of magnetic label, mediated by cell-released vesicles, complicates the picture of nanoparticles outcome in the organism and their use as MRI cell tracers.