title: Iron oxide nanoparticles induce human microvascular endothelial cell permeability through reactive oxygen species production and microtubule remodeling.
abstract: BACKGROUND
  Engineered iron nanoparticles are being explored for the development of biomedical applications and many other industry purposes. However, to date little is known concerning the precise mechanisms of translocation of iron nanoparticles into targeted tissues and organs from blood circulation, as well as the underlying implications of potential harmful health effects in human.
  
  
  RESULTS
  The confocal microscopy imaging analysis demonstrates that exposure to engineered iron nanoparticles induces an increase in cell permeability in human microvascular endothelial cells. Our studies further reveal iron nanoparticles enhance the permeability through the production of reactive oxygen species (ROS) and the stabilization of microtubules. We also showed Akt/GSK-3beta signaling pathways are involved in iron nanoparticle-induced cell permeability. The inhibition of ROS demonstrate ROS play a major role in regulating Akt/GSK-3beta - mediated cell permeability upon iron nanoparticle exposure. These results provide new insights into the bioreactivity of engineered iron nanoparticles which can inform potential applications in medical imaging or drug delivery.
  
  
  CONCLUSIONS
  Our results indicate that exposure to iron nanoparticles induces an increase in endothelial cell permeability through ROS oxidative stress-modulated microtubule remodeling. The findings from this study provide new understandings on the effects of nanoparticles on vascular transport of macromolecules and drugs.
authors.affiliation: The Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA. yqian@cdc.gov.
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Apopa
authors.forename: Yong
authors.initials: Y
authors.lastname: Qian
authors.forename: Rong
authors.initials: R
authors.lastname: Shao
authors.forename: Nancy Lan
authors.initials: NL
authors.lastname: Guo
authors.forename: Diane
authors.initials: D
authors.lastname: Schwegler-Berry
authors.forename: Maricica
authors.initials: M
authors.lastname: Pacurari
authors.forename: Dale
authors.initials: D
authors.lastname: Porter
authors.forename: Xianglin
authors.initials: X
authors.lastname: Shi
authors.forename: Val
authors.initials: V
authors.lastname: Vallyathan
authors.forename: Vincent
authors.initials: V
authors.lastname: Castranova
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Flynn