The impact of titanium dioxide nanoparticles on human lung cell lines in Vitro

Abstract

Titanium dioxide (TiO2) nanoparticles have attracted widespread use in many applications. However, emerging concerns have arisen over their consequent impact to public health and environment. Unless the toxicity of TiO2 nanoparticles towards biological systems can be assessed and potentially suppressed reliably, and the factors which govern the biological impact of the nanoparticles are better understood, the use of TiO2 nanoparticles will continue to raise concern in the general populace. Herein, the factors affecting a reliable assessment of the nanoparticle safety in an in vitro model using human lung cell lines A549 and H1299 were investigated. The choices of biological assays and type of target cell lines used in the nanotoxicity assessment have been found to affect the level of observed impact of TiO2 nanoparticles. Evidence gathered from this study suggests that both viability and metabolic assays should be carried out collectively to gain a true assessment of nanotoxicity. A549 and H1299, the epithelial cell lines from the same tissue of origin (lung), were shown to have a different level of cellular response to TiO2 nanoparticles. The effects of particle concentration, aggregate sizes, biokinetic behaviour, and surface chemistries on the nanotoxicity assessment were investigated. The aggregate size was shown to strongly influence its propensity to be taken up by A549 and H1299 cell lines. The presence of micron-sized aggregates resulted in a significant increase of cellular uptake and biological impact compared to the submicron-sized TiO2 aggregates. The biokenetic behaviour of nanoparticles, in particular its interaction with fetal bovine serum (FBS) protein, was found to affect the cellular uptake profile and their consequent impact. Although the particle uptake after a 24 h exposure was higher for the FBS-treated particles, the biological impact was lower compared to the non-FBStreated TiO2. The adsorption of FBS proteins appears to provide protection to the cells from the internalised particles. The modification of nanoparticle surface chemistry was completed by a grafting-to polymer technique, using thiol-ene click chemistry. This modification resulted in the reduction of particle size aggregates and adsorption of different types of serum proteins; therefore, lowering cellular uptake and consequent impact.