Background: The in vivo kinetics of nanoparticles is an essential to understand the hazard of nanoparticles. Here, the absorption, distribution, and excretion patterns of titanium dioxide (TiO₂) and zinc oxide (ZnO) nanoparticles following oral administration were evaluated. Methods: Nanoparticles were orally administered to rats for 13 weeks (7 days/week). Samples of blood, tissues (liver, kidneys, spleen, and brain), urine, and feces were obtained at necropsy. The level of Ti or Zn in each sample was measured using inductively coupled plasma-mass spectrometry. Results: TiO₂ nanoparticles had extremely low absorption, while ZnO nanoparticles had higher absorption and a clear dose-response curve. Tissue distribution data showed that TiO₂ nanoparticles were not significantly increased in sampled organs, even in the group receiving the highest dose (1041.5 mg/kg body weight). In contrast, Zn concentrations in the liver and kidney were significantly increased compared with the vehicle control. ZnO nanoparticles in the spleen and brain were minimally increased. Ti concentrations were not significantly increased in the urine, while Zn levels were significantly increased in the urine, again with a clear dose-response curve. Very high concentrations of Ti were detected in the feces, while much less Zn was detected in the feces. Conclusions: Compared with TiO₂ nanoparticles, ZnO nanoparticles demonstrated higher absorption and more extensive organ distribution when administered orally. The higher absorption of ZnO than TiO₂ nanoparticles might be due to the higher dissolution rate in acidic gastric fluid, although more thorough studies are needed.

The evaluation of the role of physicochemical properties in the toxicity of nanoparticles is important for the understanding of toxicity mechanisms and for controlling the behavior of nanoparticles. The surface charge of nanoparticles is suggested as one of the key parameters which decide their biological impact. In this study, we synthesized fluorophore-conjugated polystyrene nanoparticles (F-PLNPs), with seven different types of surface functional groups that were all based on an identical core, to evaluate the role of surface charge in the cellular uptake of nanoparticles. Phagocytic differentiated THP-1 cells or non-phagocytic A549 cells were incubated with F-PLNP for 4 h, and their cellular uptake was quantified by fluorescence intensity and confocal microscopy. The amount of internalized F-PLNPs showed a good positive correlation with the zeta potential of F-PLNPs in both cell lines (Pearson’s r = 0.7021 and 0.7852 for zeta potential vs. cellular uptake in THP-1 cells and nonphagocytic A549 cells, respectively). This result implies that surface charge is the major parameter determining cellular uptake efficiency, although other factors such as aggregation/agglomeration, protein corona formation, and compositional elements can also influence the cellular uptake partly or indirectly.

Background: Hazard identification for risk assessment of nanoparticles (NPs) is mainly composed ofin vitrocell-based assays andin vivoanimal experimentation. The rapidly increasing number and functionalizations of NPs makesin vivotoxicity tests undesirable on both ethical and financial grounds, creating an urgent need for development ofin vitrocell-based assays that accurately predictin vivotoxicity and facilitate safe nanotechnology.Methods: In this study, we used 9 different NPs (CeO₂, TiO₂, carbon black, SiO₂, NiO, Co₃O₄, Cr₂O₃, CuO, and ZnO). As anin vivotoxicity endpoint, the acute lung inflammogenicity in a rat instillation model was compared with thein vitrotoxicity endpoints comprising cytotoxicity, pro-inflammatory cytokine expression, or haemolytic potential. Forin vitroassays, 8 different cell-based assays were used including epithelial cells, monocytic/macrophage cells, human erythrocytes, and combined culture.Results: ZnO and CuO NPs acting via soluble toxic ions showed positive results in most of assays and were consistent with the lung inflammation data. When compared inin vitroassays at the same surface area dose (30 cm²/mL), NPs that were low solubility and therefore acting via surface reactivity had no convincing activity, except for CeO₂NP. Cytotoxicity in differentiated peripheral blood mononuclear cells was the most accurate showing 89% accuracy and 11% false negativity in predicting acute lung inflammogenicity. However, the haemolysis assay showed 100% consistency with the lung inflammation if any dose, having statistical significance was considered positivity. Other cell-basedin vitroassays showed a poorer correlation within vivoinflammogenicity.Conclusions: Based on the toxicity mechanisms of NPs, two different approaches can be applied for prediction ofin vivolung inflammogenicity. Mostin vitroassays were good at detecting NPs that act via soluble ions (i.e., ZnO and CuO NP). However,in vitroassays were limited in detecting NPs acting via surface reactivity as their mechanism of toxicity, except for the haemolysis assay.