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Predictive Models of Nanotoxicity: Relationship of Physicochemical Properties to Particle Movement Through Biological Barriers
VARMA, R. S. Predictive Models of Nanotoxicity: Relationship of Physicochemical Properties to Particle Movement Through Biological Barriers. Presented at The Scientist-to-Scientist meeting in Research Triangle Park (RTP), Raleigh-Durham, NC, June 30, 2010.
To inform the public.
Understanding the linkage between the physicochemical (PC) properties of nanoparticles (NP) and their activation of biological systems is poorly understood, yet fundamental to predicting nanotoxicity, idenitifying mode of actions and developing appropriate and effective regulatory guidelines. Particle surface charge, surface coating and “redox” activity are PC properties that critically influence NP uptake, their movement (i.e., transcytosis) through cellular barriers and their oxidative stress (OS) mediated toxicity. This research examines how the PC features of size; charge and coating influence the movement/toxicity of high risk nanomaterials (e.g., nanosilver (NanoAg), using culture models of the (human) gastrointestinal epithelial cell barrier and the (rodent) blood brain barrier (BBB). NanoAg is used in water purification, antiseptics, food products, medical devices, biocidals and numerous consumer and manufacturing products. “Green chemistry” synthesis and surface modification (SM) of this material is done to reduce their environmental burden, enhance their bioavailability and reduce their possible toxicity. Since ingestion is a dominant route of exposure for nanoAg, an in vitro “screen” has been designed to determine if parent and SM-nanoAgs can move through (i.e., translocate) the intestinal barrier and cross the BBB, thereby posing neurotoxic risk. PC properties (e.g., zeta potential, aggregate size) of these NP are being measured under experimental conditions, and correlated with their ability to cross these biological barriers and create oxidative stress (OS)-mediated (neuro) toxicity. Further analysis will determine if a causal relationship exists between the PC properties of SM-NanoAgs and their biological activation.