Repeated inhalation exposure to polystyrene nanoplastics induced sustained pulmonary injury and fibrosis in mice.

Atmospheric nanoplastics represent an emerging environmental health concern, as their small size and physicochemical properties facilitate unintentional inhalation. However, their pulmonary toxicity under repeated exposure and following exposure cessation remains poorly understood. Here, polystyrene nanoplastics (PS-NPs) with different particle sizes (25, 100, and 500 nm) were intratracheally instilled into C57BL/6 mice at doses of 1 and 5 mg/kg body weight, three times per week for four weeks (exposure period, EXP), followed by a two-week post-exposure period (PEP). A ddH₂O-treated group was included as the control. PS-NPs accumulated extensively in the lungs and translocated to the heart, liver, spleen, and kidneys. Notably, inhaled nanoplastics sustained in lung tissue after PEP. Exposure to PS-NPs disrupted the alveolar epithelial barrier, induced inflammation, and oxidative stress in lung tissue, altered lung function, led to pulmonary fibrosis, and reduced peripheral white blood cell counts. These toxic effects were particle size-dependent, with smaller particles inducing greater toxicity. Moreover, adverse effects sustained during PEP, indicating that PS-NPs-induced injury was not readily reversible in the short term. Furthermore, our results suggest that macrophage polarization is involved in the progression of PS-NPs-induced pulmonary fibrosis. These findings demonstrate that repeated inhalation exposure to PS-NPs can induce sustained pulmonary injury, with incomplete recovery observed during PEP, highlighting potential respiratory health concerns associated with airborne nanoplastics.