SiO(2) and TiO(2) nanoparticles synergistically trigger macrophage inflammatory responses

Silicon dioxide (SiO(2)) nanoparticles (NPs) and titanium dioxide (TiO(2)) NPs are the most widely used inorganic nanomaterials. Although the individual toxicities of SiO(2) and TiO(2) NPs 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 SiO(2) and TiO(2) NPs 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 SiO(2) and TiO(2) NPs. In macrophages, SiO(2) NPs localized in lysosomes and TiO(2) NPs did not; while only TiO(2) NPs 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 SiO(2) and TiO(2) NPs 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 SiO(2) and TiO(2) NPs 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12989-017-0192-6) contains supplementary material, which is available to authorized users.