Organ-specific in vitro models for prediction of hazard assessment of nanomaterials

Organ-specific multicellular in vitro models are used to mimic the lung-blood-brain axis, and to assess the nanomaterials (NMs) safety in humans. We employed a triculture lung model, a whole-blood model, an astrocytes-neurons coculture to examine health outcomes by three cerium dioxide (CeO2) NMs and silver (Ag) nanowires. Endpoints included cytotoxicity, gene expression, genotoxicity, inflammatory markers at the air–liquid interface (ALI), complement activation, and secondary toxicity in astrocytes-neurons coculture. Post-exposure, CeO2–3.5 nm high-dose decreased cell viability, no DNA damage was detected. At epithelial-macrophages interface, CeO2–50 nm upregulated surfactant protein A (SPA), cell surface death receptor (FAS), and heme oxygenase-1 (HMOX1), whereas CeO2–3.5 nm downregulated SPA. Ag-nanowires upregulated HMOX1, macrophage inflammatory protein-1β (MIP-1β), granulocyte colony-stimulator factor (G-CSF), chemokine C-X-C-motif ligand 1 (CXCL1). At endothelial side, CeO2–50 nm and − 3.5 nm, and Ag-nanowires upregulated HMOX1. In whole-blood model, CeO2–3.5 nm high-dose reduced terminal complement complex (TCC) proteins, while CeO2–50 nm and Ag-nanowires increased them. Nanomaterials activated CD11b+ on granulocytes and monocytes. Ag-nanowires conditioned-medium (CM) on astrocytes-neurons coculture, decreased cell viability. CeO2–50 nm CM upregulated IL1β, NFκB, and HMOX1. Overall, CeO₂–3.5 nm exhibits lung toxicity; CeO₂–50 nm CM triggers inflammatory response and Ag-nanowires CM may induce cytotoxicity in brain cells.