Unveiling the Pulmonary Toxicity of Polystyrene Nanoplastics: A Hierarchical Oxidative Stress Mechanism Driving Acute–Subacute Lung Injury

The ubiquitous contamination of airborne nanoplastics (<100 nm), particularly polystyrene nanoplastics (PS NPs), has emerged as critical determinant regarding respiratory health. As inhalation exposure represents a primary route of human contact, the pulmonary toxicological profiles of PS NPs remained poorly characterized, with underlying mechanisms lacking. In this study, we systematically investigated the pulmonary toxicological mechanisms of PS NPs for inducing acute-subacute lung injury. PS NPs markedly reduced cell viability of lung epithelial cells (BEAS-2B cells) and macrophages (RAW 264.7 cells) in a dose-dependent manner. Further investigations revealed that PS NPs induced a hierarchical oxidative stress paradigm that redox imbalance triggered by reactive oxygen species (ROS) burst led to the cascade activation of compensatory nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway, up-regulation of pro-inflammatory cytokines, mitochondrial dysfunction, and apoptosis. Furthermore, the in vivo toxicities of PS NPs were validated by the acute and subacute pulmonary injury on rodent models, which was characterized by obvious inflammatory cell infiltration and pulmonary fibrosis. These results indicated that hierarchical oxidative stress mediated PS NPs-induced acute-subacute lung injury. This also raised a warning that susceptible individuals with long-term plastic exposure should receive regular pulmonary monitoring.