Oropharyngeal aspirated Ag/TiO₂ nanohybrids: Transformation, distribution and toxicity

The wide application of Ag-loaded TiO₂ nanohybrids photocatalysts on environment and energy increases the lung exposure risk to humans. Ag/TiO₂ nanohybrids inhalation can cause pulmonary toxicity, and there are concerns about whether the loaded silver can be released and cause toxic effects on extrapulmonary organs. Therefore, in this study, the possible biotransformation, biodistribution, and toxicity of oropharyngeal aspirated Ag/TiO₂ nanohybrids were investigated first time in vitro and in vivo to answer this question. Firstly, the results of biotransformation showed that the ultrafine silver nanoparticles (~3.5 nm, 2 w/w%) loaded on the surface of nano-TiO₂ (~25 nm) could agglomerate and release in Gamble's solution, and the hydrodynamic diameter of the nanohybrids agglomerates increased from about 200 nm to 1 μm. Furthermore, after exposure 10 mg/kg Ag/TiO₂ nanohybrids to C57BL/6 J male mice by oropharyngeal aspiration weekly, the biodistribution results showed that the released silver could result in blood, liver, and brain distribution within 28 d. Finally, body weight, organ coefficient, blood biochemical indicators of liver and kidney function, and pathological images demonstrated that although silver could release and lead to extrapulmonary organ distribution, it did not cause obvious extrapulmonary organ damage. The original lung was still the main toxicity and accumulation target organ of Ag/TiO₂ nanohybrids, which mainly manifested as the pro-inflammatory and pro-fibrotic effects that should be focused on in the future. Therefore, this study is of great significance in evaluating the safety of Ag-loaded TiO₂ nanoparticles and predicting their toxic mechanisms.