Carbon Nanotube-Intestinal Barrier Cell Interactions, Absorption, and Dosimetry
EMSL Project ID
46891
Abstract
Carbon nanotubes (CNT) are important components of the rapidly expanding nanotechnology field. Due to their size and unique chemical, electrical, mechanical, and thermal properties, they have found widespread application in electronics, aerospace, medicine, agriculture, pharmaceutics, and other industries. The current and projected demand, production, and application of these nanoscale materials will be accompanied by proportional risk for occupational, environmental, and even clinical exposures. Despite recent efforts to characterize their potential health hazards, the overall understanding of the biological effects of CNT exposure is far from complete. The proposed work is motivated by an urgent need to understand the mechanisms that underlie CNT's potential toxicity or biocompatibility, to establish manufacturing and exposure guidelines. Cellular interactions and intracellular fate of carbon nanomaterials will drive their cellular effects and ultimately dictate their impact on human health. We are identifying these processes in an in vitro model of the intestinal barrier using CNTs with well-defined functionalization and surface properties, and correlating their cellular interactions with the biological response. Our research, which is funded by grants from the NIEHS and NIGMS, will directly contribute to the design of safer carbon nanomaterials and establishment of exposure guidelines. The central hypothesis underlying our research is that engineered CNTs (both single- and multi-walled nanotubes) that are highly dispersible in aqueous and biological systems, when exposed to gastrointestinal (GI) tract cells, will be absorbed by GI epithelia, interact with the barrier cells, partition between GI epithelia and the hepatic portal circulation, and exert effects that alter function in the gut-liver axis and beyond. We contend that the nature of these effects is dependent on the physico-chemical properties and each unique state of functionalization of the nanotubes. This represents an innovative and unique exposure route for ENMs, one that has received little attention in the toxicology community. These studies will directly contribute to the EMSL mission in supporting environmental-molecular research by specifically addressing the Science of Interfacial Phenomena theme and its focus on 'Fundamental investigations of nanoparticle interactions with biological systems.' These studies will also address the Biological Interactions and Dynamics theme by investigating the interaction dynamics of membrane proteins in response to environmental and physical perturbations posed by engineered nanomaterials.
Project Details
Project type
Exploratory Research
Start Date
2012-01-09
End Date
2013-02-12
Status
Closed
Released Data Link
Team
Principal Investigator