Abstract
Increasing concerns over the possible risks of nanotechnology necessitates breakthroughs in structure-activity relationship (SAR) analyses of engineered nanomaterials (ENMs) at nano-bio interfaces. However, current nano-SARs are often based on univariate assessments and fail to provide tiered views on ENM-induced bio-effects. Here we report a multi-hierarchical nano-SAR assessment for a representative ENM, Fe2O3, by metabolomics and proteomics analyses. The established nano-SAR profile allows the visualizing of the contributions of seven basic properties of Fe2O3 to its diverse bio-effects. For instance, although surface reactivity is responsible for Fe2O3-induced cell migration, the inflammatory effects of Fe2O3 are determined by aspect ratio (nanorods) or surface reactivity (nanoplates). These nano-SARs are examined in THP-1 cells and animal lungs, which allow us to decipher the detailed mechanisms including NLRP3 inflammasome pathway and monocyte chemoattractant protein-1-dependent signaling. This study provides more insights for nano-SARs, and may facilitate the tailored design of ENMs to render them desired bio-effects.