Work

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

Year: 2026

Type: article

Abstract: 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 (CeO 2 ) 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, CeO 2 –3.5 nm high-dose decreased cell viability, no DNA damage was detected. At epithelial-macrophages interface, CeO 2 –50 nm upregulated surfactant protein A ( SPA ), cell surface death receptor ( FAS ), and heme oxygenase-1 ( HMOX1 ), whereas CeO 2 –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, CeO 2 –50 nm and − 3.5 nm, and Ag-nanowires upregulated HMOX1 . In whole-blood model, CeO 2 –3.5 nm high-dose reduced terminal complement complex (TCC) proteins, while CeO 2 –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. CeO 2 –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. • A novel concept of replicating a complex in vitro system, the lung-blood-brain axis, interconnecting organ-specific multicellular in vitro models. • A next-generation risk assessment (NGRA) of three different types of cerium dioxide (CeO 2 ) and silver (Ag) nanomaterials, through organ-specific multicellular models. • The advanced respiratory model, the whole blood model and the astrocyte-neuronal coculture can be together employed to investigate the connection between pulmonary processes and systemic responses in the lung-blood-brain axis.

Source: Toxicology in Vitro

DOI: 10.1016/j.tiv.2026.106205