When Plastic ParticlesHit the Nose: Metabolic Responsesto Nanoplastics, Microplastics, and Their Mixtures in Normal HumanNasal Epithelial Cells

Abstract

Abstract Airborne micro- and nanoplastics are emerging inhalation contaminants, yet their effects on the first human airway barrier, the nasal epithelium, remain poorly understood. Here, we investigated metabolic responses of normal human nasal epithelial cells exposed to polystyrene nanoplastics (100 nm), microplastics (7 μm), or their mixture using comprehensive metabolomics and lipidomics of both cells and secretome analyzed by ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Nanoplastics induced the strongest intracellular perturbations, characterized by increased amino acid- and purine-related metabolites, including homocystine, uric acid, aspartic acid, and glutamic acid, together with marked depletion of membrane lipids, particularly phosphatidylcholines. The particle mixture produced partially overlapping but generally attenuated responses, whereas microplastics alone caused comparatively modest changes. This attenuation was consistent with particle characterization showing partial nanoplastic adsorption onto microplastics, which reduced the freely dispersed nanoplastic fraction in the mixture. Secretome profiling revealed distinct extracellular metabolic fingerprints, with nanoplastics and mixtures increasing metabolites linked to oxidative stress, amino acid turnover, and detoxification, while reducing several membrane-derived lipids. Pathway enrichment analysis highlighted disturbances in carbohydrate metabolism, glycerophospholipid metabolism, the pentose phosphate pathway, and amino acid and nucleotide metabolism. Overall, these findings identify normal human nasal epithelial cells as a metabolically sensitive target of plastic particle exposure and suggest that nanoplastics are primary drivers of the observed metabolic perturbations at the airway interface in vitro.