Size Dependent Neuronal Translocation of Nanoparticles

Project Information

Principal Investigator	Gunter Oberdorster
Institution	University of Rochester
Project URL	View
Relevance to Implications	High
Class of Nanomaterial	Engineered Nanomaterials
Impact Sector	Environment
Broad Research Categories	Hazard Generation, Dispersion, Transformation etc.
NNI identifier

Funding Information

Country	USA
Anticipated Total Funding	$199,997.00
Annual Funding	$66,665.67
Funding Source	NSF
Funding Mechanism	Extramural
Funding Sector	Government
Start Year	2004
Anticipated End Year	2007

Abstract/Summary

There is increasing concern about potential adverse effects of engineered nanoparticles (NP) on the environment and on human health. Because of their small size of <100 nm in diameter, NP are likely to elicit much greater biological activities than larger-sized particles. Distribution of NP from the portal of entry to other organs may induce serious adverse effects. In particular, the findings of nano-sized particles translocating via sensory neurons from the respiratory tract (nasal region) to structures of the Central Nervous System (CNS) raise questions about potential short-term and longterm health consequences. Are uptake and translocation in sensory nerves controlled by the size of NP? Does NP chemical composition and surface coating influence neuronal uptake and translocation? Does the translocation of NP induce signs of toxicity in target areas of the brain? This proposed research will address these fundamental questions within the SGER program of NSF. The research is considered exploratory and high risk because it is a first attempt to systematically examine NP size-dependent translocation along neuronal pathways, representing a project of an emerging area of nanotoxicology. Results will likely catalyze nanotechnological engineering with respect to developing nanostructured materials based on health effects.

The studies will be performed in rats using intranasal instillation of NP. The Objective 1a studies (limit of NP size for translocation) will be performed with gold nanoparticles of 5 different sizes, 2 nm . 100 nm. This will be followed by Objective 1b studies on the impact of NP chemistry using different types of NP (nanogold with different coatings; TiO2; SiO2; Cd-based quantum dots and rods and Pt-Fe core-shell nanoparticles).

This research necessitates close collaborations between materials scientists and toxicologists; the proposed studies will, therefore, be performed in a multidisciplinary team approach involving scientists in the disciplines of classical toxicology, cellular/molecular toxicology, and materials science at the University of Rochester. Results of this exploratory research will form the basis for a subsequent comprehensive research program to assess biological effects of NP, whether they are adverse or benign, and to elucidate underlying cellular and molecular mechanisms.