Sentinel supervised lung-on-a-chip: A new environmental toxicology platform for nanoplastic-induced lung injury.

Nanoplastics are prevalent in the air and can be easily inhaled, posing a threat to respiratory health. However, there have been few studies investigating the impact of nanoplastics on lung injury, especially chronic obstructive pulmonary disease (COPD). Furthermore, cell and animal models cannot deeply understand the pollutant-induced COPD. Existing lung-on-a-chip models also lack interactions among immune cells, which are crucial in monitoring complex responses. In the study, we built the lung-on-a-chip to accurately recapitulate the structural features and key functions of the alveolar-blood barrier while integrating multiple immune cells. The stability and reliability of the lung-on-a-chip model were demonstrated by toxicological application of various environmental pollutants. We Further focused on exploring the association between COPD and polystyrene nanoplastics (PS-NPs). As a result, the cell viability significantly decreased as the concentration of PS-NPs increased, while TEER levels decreased and permeability increased. Additionally, PS-NPs could induce oxidative stress and inflammatory responses at the organ level, and crossed the alveolar-blood barrier to enter the bloodstream. The expression of α1-antitrypsin (AAT) was significantly reduced, which could be served as early COPD checkpoint on the lung-chips. Overall, the lung-on-a-chip provides a new platform for investigating the pulmonary toxicity of nanoplastics, demonstrating that PS-NPs can harm the alveolar-blood barrier, cause oxidative damage and inflammation, and increase the risk of COPD.