Inhalation of Environmental Polystyrene Micro/Nanoplastics Induces Pulmonary Toxicity and Synergistically Exacerbates Acute Lung Injury in Male Mice

ABSTRACT Inhalation exposure to plastic particles has raised widespread concern for lung health. This study aimed to systematically evaluate the effects of inhaled polystyrene nanoparticles (PS‐NPs, 50 nm) and polystyrene microparticles (PS‐MPs, 1 μm) on pulmonary inflammation and lung function in healthy mice, and further investigate the superimposed effects of prior particle exposure on the severity of acute lung injury (ALI). Healthy mice underwent inhalation exposure to PS‐NPs or PS‐MPs (15 mg/kg, once daily for 14 days). Both types of particles induced mild pulmonary inflammatory infiltration (increased bronchoalveolar lavage fluid inflammatory cells, lung tissue CD68 + cell infiltration, mild alveolar septal thickening, and pulmonary interstitial inflammatory cell infiltration). Pulmonary function testing revealed that PS‐NPs induced compensatory ventilatory enhancement, significantly reduced lung compliance, and impaired parenchymal elasticity, whereas PS‐MPs primarily caused large airway obstructive dysfunction and elevated small airway resistance, with overall lung function impairment being more severe than that induced by PS‐NPs. Using an LPS‐induced ALI mouse model to assess the superimposed effects of prior exposure, the results showed that PS‐MPs pre‐exposure significantly exacerbated LPS‐induced inflammatory cell infiltration, upregulation of pro‐inflammatory cytokines ( Il1β, Il6 , and Tnfa ), and destruction of lung tissue structure, while synergistically aggravating comprehensive pulmonary dysfunction across baseline ventilation, static lung volume, lung elasticity, and both large and small airway function. In contrast, PS‐NPs pre‐exposure exhibited weaker superimposed effects compared to PS‐MPs. These findings highlight the need for a deeper understanding of the size‐dependent toxicity of inhalable plastic particles and warn of the health risks.