Dry Generation of CeO₂ Nanoparticles and Deposition onto a Co-Culture of A549 and THP-1 Cells in Air-Liquid Interface—Dosimetry Considerations and Comparison to Submerged Exposure

• Main Authors: Francesca Cappellini, Sebastiano Di Bucchianico, Venkatanaidu Karri, Siiri Latvala, Maria Malmlöf, Maria Kippler, Karine Elihn, Jonas Hedberg, Inger Odnevall Wallinder, Per Gerde, Hanna L. Karlsson
• Format: Article
• Language: English
• Published: MDPI AG 2020-03-01
• Series: Nanomaterials
• Subjects: nanotoxicology; air-liquid interface; PreciseInhale; dosimetry; inflammation; ceria
• Online Access: https://www.mdpi.com/2079-4991/10/4/618

Relevant in vitro assays that can simulate exposure to nanoparticles (NPs) via inhalation are urgently needed. Presently, the most common method employed is to expose lung cells under submerged conditions, but the cellular responses to NPs under such conditions might differ from those observed at the more physiological air-liquid interface (ALI). The aim of this study was to investigate the cytotoxic and inflammatory potential of CeO₂ NPs (NM-212) in a co-culture of A549 lung epithelial cells and differentiated THP-1 cells in both ALI and submerged conditions. Cellular dose was examined quantitatively using inductively coupled plasma mass spectrometry (ICP-MS). The role of serum and LPS-priming for IL-1β release was further tested in THP-1 cells in submerged exposure. An aerosol of CeO₂ NPs was generated by using the PreciseInhale^® system, and NPs were deposited on the co-culture using Xpose<i>ALI</i>^®. No or minor cytotoxicity and no increased release of inflammatory cytokines (IL-1β, IL-6, TNFα, MCP-1) were observed after exposure of the co-culture in ALI (max 5 µg/cm²) or submerged (max 22 µg/cm²) conditions. In contrast, CeO₂ NPs cause clear IL-1β release in monocultures of macrophage-like THP-1, independent of the presence of serum and LPS-priming. This study demonstrates a useful approach for comparing effects at various in-vitro conditions.