Grouping of Poorly Soluble Low (Cyto)Toxic Particles: Example with 15 Selected Nanoparticles and A549 Human Lung Cells.

Veno Kononenko,David B Warheit,Damjana Drobne

doi:10.3390/nano9050704

Veno Kononenko, David B Warheit + Show 1 more

Open Access

https://doi.org/10.3390/nano9050704

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Journal: Nanomaterials	Publication Date: May 6, 2019
Citations: 4	License type: CC BY 4.0

Affiliation: University of Ljubljana, Wilmington University

Abstract

Poorly soluble, low (cyto)toxic particles (PSLTs) are often regarded as one group, but it is important that these particles can be further differentiated based on their bioactivity. Currently, there are no biological endpoint based groupings for inhaled nanoparticles (NPs) that would allow us to subgroup PSLTs based on their mode of action. The aim of this study was to group NPs based on their cytotoxicity and by using the in vitro response of the endo-lysosomal system as a biological endpoint. The endo-lysosomal system is a main cellular loading site for NPs. An impaired endo-lysosomal system in alveolar type II cells may have serious adverse effects on the maintenance of pulmonary surfactant homeostasis. The 15 different NPs were tested with human lung adenocarcinoma (A549) cells. The highly soluble NPs were most cytotoxic. With respect to PSLTs, only three NPs increased the cellular load of acid and phospholipid rich organelles indicating particle biopersistence. All the rest PSLTs could be regarded as low hazardous. The presented in vitro test system could serve as a fast screening tool to group particles according to their ability to interfere with lung surfactant metabolism. We discuss the applicability of the suggested test system for bringing together substances with similar modes-of-action on lung epithelium. In addition, we discuss this approach as a benchmark test for the comparative assessment of biopersistence of PSLTs.

Highlights

Safety testing of every unique particle for their potential adverse effects is virtually impossible
The presented in vitro test system could serve as a fast screening tool to group particles according to their ability to interfere with lung surfactant metabolism
All this favors the explanation that particle solubility is the main characteristic of particles which determines their cytotoxicity, consistent with the findings of Horie et al (2012), who compared the physicochemical properties of 24 different NPs with their cellular effects in vitro on A549 cells [46]

Summary

Introduction

Safety testing of every unique particle for their potential adverse effects is virtually impossible. When performing studies on nanoparticle (NP) hazard effects, we need to consider the relevance and reliability of using experimental methods as well as legislative and ethical aspects of animal studies [1]. Utilizing in vitro methods with human cells follows the principle of the 3Rs (replacement, refinement and reduction of laboratory animals) and has the potential to improve the relevance of nanosafety assessment for humans [1]. It has been shown, for example, that rats are an inappropriate model for predicting human lung cancer risk following chronic particle overload inhalation exposures [3]. The in vitro studies are essential for the mechanistic understanding of NP-cell interactions [5]

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