Immunomodulatory activity of zinc peroxide (ZnO2) and titanium dioxide (TiO2) nanoparticles and their effects on DNA and protein integrity

摘要

Nanoparticles that are made from zinc and titanium oxide have found widespread applications, including their use in sunscreens. However, there is little information regarding their effects on immune cells. In the current study, we synthesized charge stabilized and "ligand free" colloid stable ZnO2 and TiO2 nanoparticles. Most previous published studies commonly used ZnO and TiO2 nanoparticles. In the current study we investigated the comparative toxicity of ZnO2 and TiO2 nanoparticles. Therefore, our results based on ZnO2 which is more oxidative than ZnO provides novel data on the possible toxicity of this species of nanoparticles. First, we investigated the immunomodulatory action of these nanoparticles on human peripheral blood mononuclear cells and their effects on DNA and protein integrity. A minimum concentration of ZnO2 nanoparticles of 1μg/mL inhibited the production of two inflammatory cytokines: interleukin-1-β and interleukin 6 by peripheral blood mononuclear cells in the presence of lipopolysaccharides. On the other hand, TiO2 nanoparticles at a concentration range of 0.1-100μg/mL did not present apparent toxicity to the peripheral blood mononuclear cells. ZnO2 nanoparticles at a minimum concentration of 2μg/mL caused DNA damage in vitro. TiO2 nanoparticles at a concentration range of 25-100μg/mL only caused marginal DNA damage. ZnO2 nanoparticles at a minimum concentration of 5μg/mL were capable of promoting aggregation of malate dehydrogenase, and facilitated its degradation at higher concentrations. Exposure of malate dehydrogenase to TiO2 at a concentration range of 2.5-15μg/mL did not alter the solubility of malate dehydrogenase. Altogether, our findings suggest that charge stabilized ZnO2 nanoparticles are nascent and interact with DNA and protein and may be harmful to immune cells. In addition, the propensity of ZnO2 nanoparticles to promote protein aggregation could facilitate the production of protein complexes that may interfere with normal immune functions.