Research

Iron oxide nanoparticles induce human microvascular endothelial cell permeability through reactive oxygen species production and microtubule remodeling

Patrick L Apopa^1,2 , Yong Qian¹ , Rong Shao³ , Nancy Lan Guo⁴ , Diane Schwegler-Berry¹ , Maricica Pacurari¹ , Dale Porter^1,5 , Xianglin Shi¹ , Val Vallyathan¹ , Vincent Castranova¹ and Daniel C Flynn⁶

¹  The Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA

²  MBR Cancer Center, School of Medicine, West Virginia University, Morgantown, WV 26506-9300, USA

³  Pioneer Valley Life Sciences Institute, Baystate Medical Center/University of Massachusetts at Amherst, Springfield, MA 01107, USA

⁴  MBR Cancer Center/Department of Community Medicine, School of Medicine, West Virginia University, Morgantown, WV 26506-9300, USA

⁵  Department of Physiology and Pharmacology, School of Medicine, West Virginia University, Morgantown, WV 26506, USA

⁶  The Commonwealth Medical College, Scranton, PA 18510, USA

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Particle and Fibre Toxicology 2009, 6:1doi:10.1186/1743-8977-6-1

Published:	9 January 2009

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-3β signaling pathways are involved in iron nanoparticle-induced cell permeability. The inhibition of ROS demonstrate ROS play a major role in regulating Akt/GSK-3β – 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.

Conclusion

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.