SiOand TiOnanoparticles synergistically trigger macrophage inflammatory responses.

Abstract

Silicon dioxide (SiO) nanoparticles (NPs) and titanium dioxide (TiO) NPs are the most widely used inorganic nanomaterials. Although the individual toxicities of SiOand TiONPs have been extensively studied, the combined toxicity of these NPs is much less understood. In this study, we observed unexpected and drastic activation of the caspase-1 inflammasome and production of IL-1β in mouse bone marrow-derived macrophages stimulated simultaneously with SiOand TiONPs at concentrations at which these NPs individually do not cause macrophage activation. Consistent with this, marked lung inflammation was observed in mice treated intratracheally with both SiOand TiONPs. In macrophages, SiONPs localized in lysosomes and TiONPs did not; while only TiONPs produced ROS, suggesting that these NPs induce distinct cellular damage leading to caspase-1 inflammasome activation. Intriguingly, dynamic light scattering measurements revealed that, although individual SiOand TiONPs immediately aggregated to be micrometer size, the mixture of these NPs formed a stable and relatively monodisperse complex with a size of ~250 nm in the presence of divalent cations. Taken together, these results suggest that SiOand TiONPs synergistically induce macrophage inflammatory responses and subsequent lung inflammation. Thus, we propose that it is important to assess the synergistic toxicity of various combinations of nanomaterials.