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In Vitro Vascular Toxicity of Manufactured Metal Oxide Nanoparticles: Size Profile Predicts Cellular Specificity, Delivered Dose, and Toxicity
Citation:
Polk, W., M. Odegaard, K. Cleveland, N. Coates, AND K. Dreher. In Vitro Vascular Toxicity of Manufactured Metal Oxide Nanoparticles: Size Profile Predicts Cellular Specificity, Delivered Dose, and Toxicity. Presented at Society of Toxicology, Phoenix, AZ, March 24 - 27, 2014.
Impact/Purpose:
Will be presented at the Society of Toxicology Meeting March 24-27, 2014, Phoenix, AZ. Alternative testing methods development to screen and rank of engineered nanoparticle for their vacular toxicity
Description:
Metal oxide nanoparticles (NPs) are being used in an expanding range of products and applications due to their unique physicochemical properties. In vivo biokinetic studies have demonstrated the ability of metal oxide 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 the potential systemic health effects of metal oxide NPs. To address this need, studies were undertaken to use alternative vascular toxicity test methods to screen and rank 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, respectively, following 24 h exposure to TiO2 and CeO2 NPs over a dose range of 3.2-200 g/ml. A combined statistical analysis of the data for all endothelial cell types and particles revealed that TiO2 NPs exhibited greater toxicity than CeO2 NPs. Subsequent analysis of individual NPs and cell types revealed distinct NP sensitivity profiles existed for each cell type which correlated either with the estimated delivered dose (assessed by optical properties) or with the agglomeration status of the particles (assessed by DLS). Use of particles differentially dispersed to nano- or microscale confirmed the impact of agglomeration on in vitro particle delivered dose and toxicity independent of other confounding factors. This work demonstrates that total delivered dose must be accounted for when testing NP toxicity in vitro.