Based on the Nano-QSAR model: Prediction of factors influencing damage to C. elegans caused by metal oxide nanomaterials and validation of toxic effects

Analysis of structure-activity relationships (SARs) at nano–bio interfaces is important for guiding the safe design of nanomaterials and the assessment of potential toxicity. Metal oxide (MeOx) nanomaterials are used in a wide range of applications due to their unique mechanical stability and optoelectronic properties. However, the increasing number of biosafety issues and exposure risks have led to a focus on the safety assessment of nanomaterials. Considering the wide range of MeOx nanomaterials and their various different properties, it is difficult to assess individual toxicities using traditional toxicological analyses. Nanometric quantitative structure–activity relationship (nano-QSAR) analysis offers new ideas for developing nano-informatics modeling. In this study, six physicochemical properties of 16 MeOx nanomaterials from different classes (MeO, MeO2, MeO3 and Me2O3) were standardized and ordered according to their weights based on the nano-QSAR analysis strategy to construct quasi-SMILES descriptors that can accurately measure the material property characteristics and finally achieve the prediction of material structural properties and bio-toxic effects. The modeling results suggest that the Zeta potential and the metal cation charge number of MeOx nanomaterials may be important parameters affecting the toxicity of associated materials. To further clarify the quantitative relationship between these two important properties and the final toxic endpoint, as well as the possible mechanism of damage, the toxicity mechanisms of four representative MeOx nanomaterials were further analyzed in this study using Caenorhabditis elegans. The results ultimately confirm that nanomaterials with higher absolute Zeta potential or higher metal cation charge may have the greater oxidative capacity and can cause more severe oxidative damage and free radical accumulation in nematodes via smaller uptake levels at the same survival rate. This study highlights the important influence of structural properties of MeOx nanomaterials on toxicity outcomes. Moreover, our data suggest that oxidative stress, an important mechanism of MeOx nanomaterial-induced damage, can be controlled by the material's Zeta potential and cationic charge number. This provides a novel strategy for the safe design and toxicity assessment of nanomaterials in the future.