Cell-nanoparticle stickiness and dose delivery in a multi-model in silico platform: DosiGUI.

BACKGROUND

It is well-known that nanoparticles sediment, diffuse and aggregate when dispersed in a fluid. Once they approach a cell monolayer, depending on the affinity or "stickiness" between cells and nanoparticles, they may adsorb instantaneously, settle slowly - in a time- and concentration-dependent manner - or even encounter steric hindrance and rebound. Therefore, the dose perceived by cells in culture may not necessarily be that initially administered. Methods for quantifying delivered dose are difficult to implement, as they require precise characterization of nanoparticles and exposure scenarios, as well as complex mathematical operations to handle the equations governing the system dynamics. Here we present a pipeline and a graphical user interface, DosiGUI, for application to the accurate nano-dosimetry of engineered nanoparticles on cell monolayers, which also includes methods for determining the parameters characterising nanoparticle-cell stickiness.

RESULTS

We evaluated the stickiness for 3 industrial nanoparticles (TiO - NM-105, CeO - NM-212 and BaSO - NM-220) administered to 3 cell lines (HepG2, A549 and Caco-2) and subsequently estimated corresponding delivered doses. Our results confirm that stickiness is a function of both nanoparticle and cell type, with the stickiest combination being BaSO and Caco-2 cells. The results also underline that accurate estimations of the delivered dose cannot prescind from a rigorous evaluation of the affinity between the cell type and nanoparticle under investigation.

CONCLUSION

Accurate nanoparticle dose estimation in vitro is crucial for in vivo extrapolation, allowing for their safe use in medical and other applications. This study provides a computational platform - DosiGUI - for more reliable dose-response characterization. It also highlights the importance of cell-nanoparticle stickiness for better risk assessment of engineered nanomaterials.