At present, safety evaluation standards for nanofood additives are made based on the toxic effects of a single additive. Since the size, surface properties and chemical nature influence the toxicity of nanomaterials, the toxicity may have dramatically changed when nanomaterials are used as food additives in a complex system. Herein, we investigated the combined toxicity of zinc oxide nanoparticles (ZnO NPs) and vitamin C (Vc, ascorbic acid). The results showed that Vc increased the cytotoxicity significantly compared with that of the ZnO only NPs. When the cells were exposed to ZnO NPs at a concentration less than 15 mg L(-1), or to Vc at a concentration less than 300 mg L(-1), there was no significant cytotoxicity, both in the case of gastric epithelial cell line (GES-1) and neural stem cells (NSCs). However, when 15 mg L(-1) of ZnO NPs and 300 mg L(-1) of Vc were introduced to cells together, the cell viability decreased sharply indicating significant cytotoxicity. Moreover, the significant increase in toxicity was also shown in the in vivo experiments. The dose of the ZnO NPs and Vc used in the in vivo study was calculated according to the state of food and nutrition enhancer standard. After repeated oral exposure to ZnO NPs plus Vc, the injury of the liver and kidneys in mice has been indicated by the change of these indices. These findings demonstrate that the synergistic toxicity presented in a complex system is essential for the toxicological evaluation and safety assessment of nanofood.

Application of nanotechnology and nanomaterials in cancer therapeutics has attracted much attention in recent years. Nano titanium dioxide is one of the most important inorganic functional materials. Cellular toxicity of pH-controlled antitumor drug release system of titanium dioxide nanotubes (TiO2-NTs) in pancreatic cancer cells (SW1990) was evaluated in this paper. The anticancer drug, doxorubicin (DOX) was easily loaded on TiO2-NTs through adsorption forces because of its high specific surface area and perfect surface activity. The drug release from the nanotubes was pH dependent. The toxicological effects were studied after co-incubation of SW1990 with TiO2-NTs-DOX, TiO2-NTs and DOX, respectively. The cellular effect of DOX released from the TiO2-NTs-DOX was same as when DOX was used alone, indicating that the synthesized TiO2-NTs are well qualified as drug carriers in antitumor drug controlled-release system.

TiO(2) nanotubes (TiO(2)-NTs) are currently attracting a high interest because the intrinsic properties of TiO(2) provide the basis for many outstanding functional features. Herein, we focus on the cytotoxicity and sublocation of TiO(2)-NTs in neural stem cells (NSCs). The cytotoxicity of TiO(2)-NTs is investigated using the methyl tetrazolium cytotoxicity and reactive oxygen species assay, the apoptosis assay by flow cytometry. Cell viability assay shows that TiO(2)-NTs inside cells are nontoxic at the low concentration. A time-dependent relationship is observed, while a dose-dependent relationship is seen only at the concentration higher than 150 μg/ml. The uptake happens shortly after incubation with cells. TiO(2)-NTs can easily pass through the cell membrane and enter into the cells. The uptake amount is increased with prolonging incubation time and reach to maximum at 48 h. Transmission electron microscopy and confocal is used to study subcellular location of TiO(2)-NTs. It is found that TiO(2)-NTs traversed cell membrane and localized in many vesicles (endosomes and lysosomes) and cytoplasm. TiO(2)-NTs in NSCs firstly disperse or metabolism by lysosomal enzymes and then exocytosis from NSCs.

Caseinophosphopeptides can protect GES-1 cells against the zinc oxide nanoparticles induced injury through the down-regulation of oxidative stress.