35 2D-Hexagonal Boron Nitride and Lung Exposure: Exploring Long-Term Effects in Healthy Versus Asthmatic Human Lung in Vitro Model

Abstract

Abstract Inhalation is one of the most pertinent routes of exposure to nanoscale materials in occupational settings. Hexagonal boron nitride (hBN) is an emerging 2D material attracting significant attention due to its superior electrical, chemical, and thermal properties. For a successful commercial application of 2D-hBN, it is of key importance to understand their safety in occupational settings. However, long-term toxicity profile of this material is largely unknown. Here, an investigation of how 2D-hBN (obtained from Graphene Flagship consortium) interacts with lung cells of healthy versus diseased individuals has been performed. We used air−liquid interface-based exposure models to investigate the potential long-term toxicity of 2D-hBN in human lung airway epithelial cells (Calu-3) and 3D reconstituted airway epithelia (MucilairTM) of healthy and asthmatic subjects. Our results revealed that 2D-hBN was taken up by cells but did not trigger cytotoxicity at occupationally relevant repeated dose exposure for five weeks. However, screening of an immuno-cytokine/chemokine panel indicated an enhanced release of certain cytokines after exposure to 2D-hBN. In addition, we observed a pronounced intracellular accumulation of lipids in lipid droplets after exposure to 2D-hBN. Since lipid intermediates can play important roles in immune-cell activation and the development of lung diseases, we are currently analysing whether 2D-hBN induces alterations in lipid composition in healthy and asthmatic cells by applying global lipidomic profiling. Overall, our data indicate a potential correlation of certain lipid accumulation with enhanced immune signaling, highlighting the need for further studies to understand if 2D-hBN can sensitize for or aggravate pulmonary diseases.