An Integrated In Vitro–In Silico Approach for Silver Nanoparticle Dosimetry in Cell Cultures

Abstract

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.

Current Strategies in Assessment of Nanotoxicity: Alternatives to In Vivo Animal Testing

“…In order to reduce the use of animal testing, humane experimental techniques have been employed to investigate biological and pathological effects as alternative forms of nanomaterial toxicity assessments. In this review, we introduce that in vitro cell-based models and in silico computational models are the most commonly used alternative testing tools to evaluate the safety and toxicity of chemical substances in the field of nanotechnology (Figure 1) [14][15][16].…”

Breathing in vitro: Designs and applications of engineered lung models

“…In this context, the ability to aerosolize particles is a must for investigating the interactions between cells and inhaled particles, as is the ability to accurately dose the amount of material coming in contact with the cells. 217 As discussed in the section on exposure systems, there are commercial devices that meet such characteristics and are becoming standards for toxicology, including the testing of cigarette and tobacco products, since in these cases a high level of reproducibility is demanded. Moreover, the requirement for reproducibility reflects the favored use of commercial 3D cell models in several of the studies reported in the section on exposure systems and summarized in Table 4.…”

An integrated pipeline and multi-model graphical user interface for accurate nano-dosimetry

“…A proper definition of the cytotoxic “potential” of a specific NP would require correlating harmful effects to the cumulative amount of material effectively interacting with cells during the exposure test, or what we refer to as the “effective dose” [9], [10]. Cells in culture are known to be sensitive to NPs (and their dissolved ions) that are internalized or even in their immediate vicinity.…”