TY - JOUR A2 - Porte, Cinta AU - Mukherjee, Dwaipayan AU - Royce, Steven G. AU - Sarkar, Srijata AU - Thorley, Andrew AU - Schwander, Stephan AU - Ryan, Mary P. AU - Porter, Alexandra E. AU - Chung, Kian Fan AU - Tetley, Teresa D. AU - Zhang, Junfeng AU - Georgopoulos, Panos G. PY - 2014 DA - 2014/10/09 TI - ModelingIn Vitro银纳米粒子SP - 85细胞反应2890 VL - 2014 AB - Engineered nanoparticles (NPs) have been widely demonstrated to induce toxic effects to various cell types. In vitrocell exposure systems have high potential for reliable, high throughput screening of nanoparticle toxicity, allowing focusing on particular pathways while excluding unwanted effects due to other cells or tissue dosimetry. The work presented here involves a detailed biologically based computational model of cellular interactions with NPs; it utilizes measurements performed in human cell culture systems in vitro, to develop a mechanistic mathematical model that can support analysis and prediction of in vivoeffects of NPs. The model considers basic cellular mechanisms including proliferation, apoptosis, and production of cytokines in response to NPs. This new model is implemented for macrophages and parameterized using in vitromeasurements of changes in cellular viability and mRNA levels of cytokines: TNF, IL-1b, IL-6, IL-8, and IL-10. The model includes in vitrocellular dosimetry due to nanoparticle transport and transformation. Furthermore, the model developed here optimizes the essential cellular parameters based on in vitromeasurements, and provides a “stepping stone” for the development of more advanced in vivomodels that will incorporate additional cellular and NP interactions. SN - 1687-8191 UR - https://doi.org/10.1155/2014/852890 DO - 10.1155/2014/852890 JF - Journal of Toxicology PB - Hindawi Publishing Corporation KW - ER -