  Potential human and environmental hazards resulting from the exposure of
living organisms to silver nanoparticles (Ag NPs) have been the subject of
intensive discussion in the last decade. Despite the growing use of Ag NPs in
biomedical applications, a quantification of the toxic effects as a function of
the total silver mass reaching cells (namely, target cell dose) is still
needed. To provide a more accurate dose-response analysis, we propose a novel
integrated approach combining well-established computational and experimental
methodologies. We first used the particokinetic model (ISD3) proposed by Thomas
and colleagues (2018) for providing experimental validation of computed Ag NP
sedimentation in static-cuvette experiments. After validation, ISD3 was
employed to predict the total mass of silver reaching human endothelial cells
and hepatocytes cultured in 96 well plates. Cell viability measured after 24h
of culture was then related to this target cell dose. Our results show that the
dose perceived by the cell monolayer after 24 h of exposure is around 85% lower
than the administered nominal media concentration. Therefore, accurate
dosimetry considering particle characteristics and experimental conditions
(e.g., time, size and shape of wells) should be employed for better
interpreting effects induced by the amount of silver reaching cells.

Tissues and Organs;Quantitative Methods