Liver injury induced by thirty- and fifty-nanometer-diameter silica nanoparticles.

Nano-size silica material is a promising reagent for disease diagnosis, cosmetics, and the food industry. For the successful application of nanoparticle materials in bioscience, evaluation of nano-size material toxicity is important. We previously found that nano-size silica particles caused acute liver failure in mice. However, the hepatotoxicity of nanosilica particles with the diameter of 70 nm or less is unknown. Here, we investigated the relationship between particle size and toxicity using nanosilica particles with diameters of 30, 50, and 70 nm (SP30, SP50, and SP70, respectively). We observed dose-dependent increases in hepatic injury following administration of SP50 and SP30, with SP30 causing greater acute liver injury than that seen with SP50. Smaller silica nanoparticles induced liver injury even at proportionally lower dose levels. Furthermore, we investigated the combinatorial toxicity of SP30 in the presence of chemically induced liver injury (including that caused by carbon tetrachloride, paraquat, cisplatin, and acetaminophen). We observed that particles of the smallest size tested (SP30) synergized with chemical substances in causing liver injury. These data suggest that the size (diameter) of the silica nanoparticles affects the severity of nanoparticle-induced liver injury, a finding that will be useful for future investigations in nanotechnology and nanotoxicology.