Environmentally relevant aged nanoplastics amplify oxidative stress-associated inhalation toxicity and delay lung clearance.

Airborne micro- and nanoplastics are emerging environmental contaminants of increasing concern, yet their inhalation toxicity and pulmonary fate remain insufficiently understood. In this study, we investigated how particle morphology and surface oxidation influence pulmonary inflammation and clearance using environmentally relevant, size-controlled polystyrene (PS) nanoplastics. Spherical and fragmented PS were generated via bottom-up and top-down approaches, respectively, and subjected to ultraviolet irradiation to simulate environmental aging. Fragmented and ultraviolet (UV)-aged nanoplastics exhibited enhanced surface oxidation and a higher intrinsic oxidative potential than pristine spherical particles. Following a single pulmonary exposure in mice via pharyngeal aspiration at doses of 25-100 μg per mouse, these environmentally transformed nanoplastics induced more severe acute pulmonary inflammation. In particular, UV-aged fragmented PS (100 μg per mouse) increased neutrophil counts by 3.9-fold compared with pristine spherical PS, along with increased pro-inflammatory cytokine production, which was closely associated with particle-derived oxidative reactivity. Although acute inflammatory responses were largely reversible, time-course analysis of lung burden after a single non-overload exposure (25 μg per mouse) revealed delayed pulmonary clearance of fragmented nanoplastics relative to spherical particles, with estimated clearance half-lives of 13.5 days for pristine spherical PS and 27.4 days for UV-aged fragmented PS. Overall, this study demonstrates that nanoplastics most relevant to real-world environmental exposure may pose a greater risk of respiratory health effects, along with prolonged lung residence.