Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu 210009, China.
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu 210096 China.
J Hazard Mater. 2023 Sep 15;458:131962. doi: 10.1016/j.jhazmat.2023.131962. Epub 2023 Jun 29.
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.
纳米塑料普遍存在于空气中，容易被吸入，对呼吸系统健康构成威胁。然而，目前关于纳米塑料对肺部损伤，尤其是慢性阻塞性肺疾病（COPD）影响的研究较少。此外，细胞和动物模型并不能深入了解污染物引起的 COPD。现有的肺芯片模型也缺乏免疫细胞之间的相互作用，而这在监测复杂反应中至关重要。在这项研究中，我们构建了肺芯片，以在整合多种免疫细胞的同时，准确再现肺泡-血管屏障的结构特征和关键功能。通过对各种环境污染物的毒理学应用，证明了肺芯片模型的稳定性和可靠性。我们进一步专注于探索 COPD 与聚苯乙烯纳米塑料（PS-NPs）之间的关联。结果表明，随着 PS-NPs 浓度的增加，细胞活力显著降低，而 TEER 水平降低，通透性增加。此外，PS-NPs 可以在器官水平诱导氧化应激和炎症反应，并穿过肺泡-血管屏障进入血液。α1-抗胰蛋白酶（AAT）的表达明显减少，这可以作为肺芯片上 COPD 的早期检测点。总的来说，肺芯片为研究纳米塑料的肺部毒性提供了一个新平台，表明 PS-NPs 可以损害肺泡-血管屏障，引起氧化损伤和炎症，并增加 COPD 的风险。
