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Development of an In Vitro Test and a Prototype Model to Predict Cellular Penetration of NanoparticlesEPA Grant Number: R833856
Title: Development of an In Vitro Test and a Prototype Model to Predict Cellular Penetration of Nanoparticles
Investigators: Chen, Yongsheng , Capco, David , Chen, Zhongfang , Crittenden, John C. , Seifert, Gotthard
Current Investigators: Chen, Yongsheng , Capco, David , Chen, Zhongfang
Institution: Arizona State University - Main Campus , Technische Universität at Dresden , University of Georgia
Current Institution: Arizona State University - Main Campus , Georgia Institute of Technology - Main Campus , University of Puerto Rico - Rio Piedras Campus
EPA Project Officer: Karn, Barbara
Project Period: July 1, 2008 through June 30, 2011
Project Amount: $399,628
RFA: Exploratory Research: Nanotechnology Research Grants Investigating Fate, Transport, Transformation, and Exposure of Engineered Nanomaterials: A Joint Research Solicitation - EPA, NSF, & DOE (2007) RFA Text | Recipients Lists
Research Category: Nanotechnology , Safer Chemicals
Testing in vivo all the potential biological effects of the anticipated large number of nanoscale products is impossible because the time and expense would be considerable. Accordingly, an urgent need exists to develop both a systematic short-term in vitro test that can predict the toxicity of nanoparticles (NPs) and computational toxicological tools that can predict NP toxicity from their physicochemical properties. In this study, we will focus on the penetration of NPs into and their pathological effects on epithelial cell layers because epithelial cells represent the body’s first line of defense against the introduction of NPs and other potentially harmful materials. An interdisciplinary team consisting of environmental engineers, a cell biologist and toxicologist, and a computational chemist has been assembled to systematically evaluate cellular responses to NPs with varied morphology, surface chemistry, and composition (including coatings and metals); and, thus to develop the test and tools described above. The ultimate goal of this project is to comprehensively integrate such data into a structure/activity paradigm or algorithm so that NP penetration of and pathology to epithelial cells can be predicted from their physicochemical parameters.
To develop a robust predictive method, we will first synthesize a variety of NPs with different sizes and shapes to use in tests. The complete set of NP properties, including size, particle size distribution, shape, particle number, morphological features (e.g., crystallinity, porosity, and surface roughness), surface area, dispersion state, surface chemistry, and other physicochemical properties, will be characterized. In addition, quantum and other parameters that may play important roles but cannot be obtained from experimental tests will be determined using computational chemistry. These properties will serve, in part, as inputs to computational toxicological models. The synthesized materials will be evaluated using the biological response test protocol developed during our previous EPA-funded project. This protocol uses a tiered in vitro testing scheme to explore cellular uptake and translocation mechanisms. As a starting point, we propose to develop a prototype computational toxicity model using modern data mining techniques such as linear and non-linear methods, neural networks, and probabilistic methods.
This research will aid in developing a common language that describes NPs and their characteristics. The outcomes will set the stage for correlating the properties of nanoparticles with their impact on epithelial cells and ultimately their biological fate and toxicity. The proposed work will allow us to better understand how the physicochemical properties of NPs determine their interactions with cells in terms of their attachment, uptake, intracellular localization, and the mechanism of toxicity in different organs in the human body. As a result, we will be able not only to provide a useful methodology for evaluating the risk of NPs, but also to provide information about their undesirable properties and ways to avoid them.