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Assessing the Effects of Silver Nanoparticles on ARPE-19 Cells via Imaging-Based High Throughput Phenotypic Profiling
Citation:
Byrd, G., A. Goldstein-Plesser, J. Nyffeler, C. Willis, A. Fisher, W. Boyes, AND J. Harrill. Assessing the Effects of Silver Nanoparticles on ARPE-19 Cells via Imaging-Based High Throughput Phenotypic Profiling. American Society for Cellular and Computational Toxicology (ASCCT) Annual Meeting, Chapel Hill, NC, October 19 - 21, 2022. https://doi.org/10.23645/epacomptox.23504424
Impact/Purpose:
Poster presented to the American Society for Cellular and Computational Toxicology (ASCCT) Annual Meeting October 2022
Description:
Increasing commercialization of silver nanoparticles (AgNPs) has resulted in elevated opportunity for human exposure and outpaced traditional risk assessment approaches that rely on in vivo testing. Therefore, efficient methods are needed to evaluate potential hazards of AgNPs. Previous studies identified particle size and surface charge as determinants of AgNP toxicity, which has primarily been attributed to reactive oxygen species generation. Those studies have generally focused on cytotoxicity or targeted cellular effects, potentially missing critical sub-cytotoxic effects that could inform risk assessment. Thus, high throughput phenotypic profiling (HTPP) was used to characterize the effects of 12 distinct AgNPs (≤ 30 µg/mL) on organelle morphology in human retinal pigmented epithelial cells (ARPE-19). Three coatings (branched polyethyleneimine, polyvinylpyrrolidone, citrate) were selected for their distinct surface charges and tested in 4 different sizes (20, 40, 60, 100 nm) to determine the effects of these properties on toxicity. The HTPP assay was run in conjunction with a transcriptomic profiling experiment involving 60 nm particles of all coating types. This facilitated evaluation of mechanisms of action underlying observed morphological effects. A cell viability and apoptosis assay was run in parallel and used to exclude cytotoxic treatments from phenotypic and transcriptomic analyses. HTPP revealed concentration-dependent emergence of sub-cytotoxic phenotypic profiles that clustered by coating type, suggesting surface charge to be more influential than particle size in the determination of AgNP toxicity. The transcriptomic data highlighted oxidative stress and cell cycle alterations as fundamental underlying toxicity mechanisms of AgNPs. This abstract does not necessarily reflect US EPA policy.
URLs/Downloads:
DOI: Assessing the Effects of Silver Nanoparticles on ARPE-19 Cells via Imaging-Based High Throughput Phenotypic Profiling
ASCCT POSTER_GB22 _V7.PDF (PDF, NA pp, 2242.421 KB, about PDF)