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Manufactured Metal Oxide Nanoparticles In Vitro Vascular Toxicity: Role of Size Profile and Cellular Specificity on Delivered Dose and Cytotoxicity
Citation:
Polk, W., K. Cleveland, M. Odegaard, N. Coates, AND K. Dreher. Manufactured Metal Oxide Nanoparticles In Vitro Vascular Toxicity: Role of Size Profile and Cellular Specificity on Delivered Dose and Cytotoxicity. Society of Toxicology, San Diego, CA, March 22 - 26, 2015.
Impact/Purpose:
Results demonstrate that nanoparticle biological delivered dose, degree of NP agglomeration, and endothelial cell type is absolutely required when assessing NP vascular toxicity in vitro.
Description:
Metal oxide nanoparticles (NPs) are used in a range of products and applications due to their unique physicochemical properties. In vivo studies have demonstrated the ability of NPs to translocate to the distal organs, including the cardiovascular system, following various routes of exposure. Therefore, it is essential that vascular toxicity be incorporated into characterizing NP systemic health effects. Our studies were undertaken to assess the vascular toxicity of 15 different metal oxides (8 TiO2 and 7 CeO2) NPs using human primary endothelial cells derived from aorta, coronary artery, lung microvasculature and umbilical cord. Endothelial cell viability and proliferation was assessed by WST-1 and cell counts following 24 h exposure to TiO2 and CeO2 NPs over a dose range of 3.2-200 µg/ml. NP cellular uptake was determined optically and NP agglomeration determined by DLS. Statistical analysis of all data from all endothelial cell subtypes and particles revealed that TiO2 NPs exhibited greater cytotoxicity than CeO2 NPs and correlated with cellular uptake. However, data analysis of individual NPs and cell types revealed distinct NP cytotoxicity profiles existed for each type of endothelial cell and regulated by NP agglomeration. For example, dispersed 10 nm TiO2 NPs were more cytotoxic to coronary endothelial cells at lower delivered dose when compared to aggregates of this same NP independent of other confounding factors. Our results demonstrate that NP biological delivered dose, degree of NP agglomeration, and endothelial cell type must be accounted for when assessing NP vascular toxicity in vitro.