Fig. 7

Contrast-inverted HAADF-STEM cross-sectional electron micrographs showing nanoparticle uptake in the 2D and 3D assays: Images were taken at the harvest time-point for the 300 μg/mL (2D) and equivalent 3D (450 μg) exposures. 16 nm-SiO₂ (a – i); 85 nm-SiO₂ (j – r). The inset light micrographs (left) show the position of the electron micrographs/particles (indicated, red outlines) in context of the complete tissue cross-section after dosing cell cultures (2D) or 3D tissue models via the in-medium or topical exposure routes (presented in triplicate by row). Magnified regions (green / blue outlines) are indicated on the low magnification images (left column, black outlines) where applicable. Alternative dose metrics including the 3D equivalent total mass doses with area (topical exposures) and volume (in-medium exposures) unit components are provided in Table 2