Multi-hierarchical Profiling the Structure-Activity Relationships of Engineered Nanomaterials at Nano-Bio Interfaces

Increasingly raised concerns (nanotoxicity, clinical translation, etc ) on nanotechnology require breakthroughs in structure-activity relationship (SAR) analyses of engineered nanomaterials (ENMs) at nano-bio interfaces. However, current nano-SAR assessments failed to disclosure sufficient information to understand ENM-induced bio-effects. Here we developed a multi-hierarchical nano-SAR assessment for a representative ENM, Fe 2 O 3 by systematically examining cellular metabolite and protein changes. This nano-SAR profile allows visualizing the contributions of 7 basal properties of Fe 2 O 3 to their diverse bio-effects. For instance, while surface reactivity is responsible for Fe 2 O 3 -induced cell migration, the inflammatory effects of Fe 2 O 3 nanorods and nanoplates are determined by their aspect ratio and surface reactivity, respectively. We further discovered the detailed mechanisms, including NLRP3 inflammasome pathway and monocyte chemoattractant protein-1 involved signaling. Both effects were further validated in animal lungs. Our findings provide substantial new insights at nano-bio interfaces, which may facilitate the tailored design of ENMs to endow them with desired bio-effects.