In Vitro Response of Immune Cells on Metal Oxide Nanoparticles with Different Solubility

In this study, three engineered metal oxide nanoparticles (NPs) with similar size but significantly different solubility were used to study the cellular uptake, toxicity and immune activation of Raw 264.7 cells. Commercially available TiO2, Fe2O3 and ZnO NPs were used in this study. Although the size of three pristine NPs are different, all three NPs showed similar aggregation state (250-300 nm) and surface zeta potential (-10 mV) in serum containing cell culture medium due to the surface adsorption of proteins. The ZnO NPs release high concentration of Zn2+ in cell culture medium, especially at lower pH mimicking endosomal environment. In contrast, Fe2O3 NPs have limited solubility and TiO2 NPs only release very low concentration of ions. The cellular loading of the TiO2 and Fe2O3 NPs increased with the incubation time and Raw264.7 cells ingested more Fe2O3 NPs than TiO2 NPs. In general, the TiO2 and Fe2O3 NPs did not have obvious cytotoxicity. However, the TiO2 and Fe2O3 NPs can induce strong immune response of Raw264.7 cells, leading to higher expression of TNF-alpha and IL-6, especially at relatively longer incubation time. ZnO NPs were rapidly ingested into cells and release Zn2+, inducing significant cell death. They also can enhance the expression of TNF-alpha and IL-6 of Raw264.7 cells at beginning, but reduced significantly at longer incubation time due to cell death.