Iron oxide nanoparticles can cross plasma membranes.

Iron deficiency is a major global public health problem despite decades of efforts with iron supplementation and fortification. The issue lies on the poor tolerability of the standard of care soluble iron salts, leading to non-compliance and ineffective correction of iron-deficiency anaemia. Iron nanoformulations have been proposed to fortify food and feed to address these issues. Since it was just postulated that some nanoparticles (NPs) might cross the plasma membrane also by a non-endocytotic pathway gaining direct access to the cytoplasm, we have studied iron NP uptake under this perspective. To this aim, we have used a recently tested protocol that has proven to be capable of following the cytoplasmic changes of iron concentration dynamics and we have demonstrated that iron oxide NPs, but not zerovalent iron NPs nor iron oxide NPs that were surrounded by a protein corona, can cross plasma membranes. By electrophysiology, we have also shown that a small and transient increase of membrane conductance parallels NP crossing of plasma membrane.