Investigating Toxicity of Airborne Metal Nanoparticles: Mechanisms and Characterization

Nanoparticle (NP, -based technologies are finding applications in fields as diverse as electronics, alternative energy, cosmetics and biomedicine, and hold great promise as new therapeutic and diagnostic tools and as effective drug delivery devices. At the same time, rising concerns that human exposure to NPs may lead to significant adverse toxic effects need to be investigated as a matter of urgency. Airborne metal-based NPs are of particular concern because they are readily suspended in ambient air and so can be inhaled incidentally or accidentally throughout their production and use. Inhaled NPs have a very high deposition efficiency in the pulmonary region, and a high propensity to penetrate the epithelium and reach interstitial sites and the circulatory system. It then follows that NP exposure could pose a risk of cardiopulmonary injury, but this type of study requires a systems-based approach. Until now, the lack of an appropriate cell-NP exposure system has hampered the study of the cardiopulmonary toxicity of inhalation exposure to metal NPs.

The long-term goal of my research program is to better understand how airborne metal-based NPs interact with biological systems by elucidating the cellular and molecular mechanisms underlying NP toxicity using an innovative toxicology approach. This program has two overarching objectives: to i) advance an in vitro toxicity testing system to screen, rank and predict with greater certainty the toxic effects of NPs and ii) identify and characterize the causal factors and NP toxicity using a toxicogenomic approach. Over the next five years, my short-term objectives will assess the toxicity of inhaled metal NPs and prioritize NPs for more in depth in animal studies by providing more information on its causal factors and mechanisms. I specifically propose to: 1) elucidate the underlying causes and mechanisms by which NPs enhance lung bacterial infection and 2) assess the effects of pulmonary NP exposure on the cardiovascular system.

With successful completion of this research, there will be many benefits providing (1) HQP with unique training opportunities for a new branch of science (nanotoxicology); (2) valuable information on the rank of NP toxicity and prioritization of NPs for in vivo testing as a cost-effective screening; (3) understanding of the mechanisms by which NP exposures produce biological responses as this will put us in a strong position to develop strategies to design safe NPs.