High Intracellular Iron Oxide Nanoparticle Concentrations Affect Cellular Cytoskeleton and Focal Adhesion Kinase-Mediated Signaling

Iron oxide nanoparticle internalization exerts detrimental effects on cell physiology for a variety of particles, but little is known about the mechanism involved. The effects of high intracellular levels of four types of iron oxide particles (Resovist, Endorem, very small organic particles, and magnetoliposomes (MLs)) on the viability and physiology of murine C17.2 neural progenitor cells and human blood outgrowth endothelial cells are reported. The particles diminish cellular proliferation and affect the actin cytoskeleton and microtubule network architectures as well as focal adhesion formation and maturation. The extent of the effects correlates with the intracellular concentration (= iron mass) of the particles, with the biggest effects for Resovist and MLs at the highest concentration (1000 µg Fe mL−1). Similarly, the expression of focal adhesion kinase (FAK) and the amount of activated kinase (pY397‐FAK) are affected. The data suggest that high levels of perinuclear localized iron oxide nanoparticles diminish the efficiency of protein expression and sterically hinder the mature actin fibers, and could have detrimental effects on cell migration and differentiation. Cell signaling pathways are affected by high intracellular nanoparticle concentrations, as shown by the reduction in cell‐cycle progression with increasing amounts of Resovist, Endorem, magnetoliposomes, and very small organic particles. Higher uptake levels lead to reduced cell proliferation along with remodeling of the actin cytoskeleton, microtubules, focal adhesion complexes, and reduced focal adhesion kinase expression and activation.