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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.