Combinatorial toxicity of ZnO and TiO2 nanoparticles in human primary epidermal keratinocytes

Abstract

Nanotoxicology encapsulates studying the interactions nanomaterials can have with biological systems and the environment. Recently, this field has gained momentum due to the influx of new nanomaterials, many of which have already become popular components of consumer products like cosmetics. Some of these applications use combinations of nanomaterials; dual nanoparticle systems. However, almost all the studies to date have focused on evaluating the toxicology of single nanomaterials. Since dual nanoparticle systems are often used due to a synergistic or antagonistic relationship between the two materials, it is only logical to expect such an interplay to trickle into their combinatorial toxic influence. This study is focused on investigating the toxicity of the dual nanoparticle system of ZnO and TiO2, which is most common in sunscreens. The combined effect of the two nanoparticles was studied using skin-mimicking human primary epidermal keratinocytes as the in vitro model. Various cellular processes were evaluated including cell death, ROS generation and DNA damage. These were linked to nanoparticle properties which were heavily characterized in terms of size, shape, solubility, zeta potential, etc. It was found that individual TiO2 nanoparticles induced low cytotoxicity even at higher concentrations while ZnO nanoparticles caused a high degree of cell death even at lower concentrations. The reason behind this difference was the solubility of ZnO nanoparticles which allowed intracellular Zn2+ ion concentration to be imbalanced inducing cell death, ROS generation and sharp DNA damage. Interesting, TiO2 nanoparticles demonstrated an ability to adsorb Zn2+ ions onto their negative surface and caused a reduction of intracellular Zn2+ ion concentration when treated alongside ZnO nanoparticles. This antagonism caused a substantial decrease in cytotoxicity and genotoxicity of the dual nanoparticle system. Intracellular TiO2 nanoparticles were singled out as the “vigilante” causing this reduction in toxicity.