title: High intracellular iron oxide nanoparticle concentrations affect cellular cytoskeleton and focal adhesion kinase-mediated signaling.
abstract: 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 microg 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.
authors.affiliation: Subfaculty of Medicine, Katholieke Universiteit Leuven, Interdisciplinary Research Centre, KUL-Campus Kortrijk, Lab BioNanoColloids, E. Sabbelaan 53, 8500 Kortrijk, Belgium.
authors.forename: Stefaan J H
authors.initials: SJ
authors.lastname: Soenen
authors.forename: Nele
authors.initials: N
authors.lastname: Nuytten
authors.forename: Simon F
authors.initials: SF
authors.lastname: De Meyer
authors.forename: Stefaan C
authors.initials: SC
authors.lastname: De Smedt
authors.forename: Marcel
authors.initials: M
authors.lastname: De Cuyper
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects* / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005290:Ferric Compounds / Q000494:pharmacology*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism*; D022001:Focal Adhesions / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism*; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D010316:Particle Size; D015398:Signal Transduction / Q000187:drug effects*; D013194:Staining and Labeling; D013499:Surface Properties / Q000187:drug effects
chemical_list: D000199:Actins; D005290:Ferric Compounds; C000499:ferric oxide; D051416:Focal Adhesion Protein-Tyrosine Kinases