Zinc oxide (ZnO) nanoparticles (NPs) are used as zinc supplements due to the nutritional value of Zn. The toxicity of ZnO NPs in the food industry is required to be elucidated because they have large surface area and high reactivity compared with bulk-sized materials and have potentials to interact with food matrices, which may lead to different biological responses. In this study, interactions between ZnO NPs and food proteins (albumin, casein, and zein) were evaluated by measuring changes in physicochemical property, fluorescence quenching ratios, and structural protein stability compared with ZnO interaction with glucose, the most interacted saccharide in our previous report. The interaction effects on cytotoxicity, cellular uptake, intestinal transport, toxicokinetics, and acute oral toxicity were also investigated. The results demonstrate that interaction between ZnO and albumin reduced hydrodynamic diameters, but increased cytotoxicity, cellular uptake, and intestinal transport in a similar manner to ZnO interaction with glucose, without affecting primary structural protein stability and toxicokinetic behaviors. Hematological, serum biochemical, and histopathological analysis reveal no toxicological findings after orally administered ZnO NPs interacted with albumin or glucose in rats for 14 consecutive days, suggesting their low oral toxicity. In conclusion, the interactions between ZnO NPs and food proteins modulate in vitro biological responses, but do not affect in vivo acute oral toxicity. Further study is required to ascertain the interaction effects on chronic oral toxicity.
