Polypropylene Nanoplastic Exposure to Respiratory Epithelial Barrier‐On‐Chip and Interfacial Interactions With Human Serum Albumin

ABSTRACT Under the influence of environmental pollution, chronic non‐communicable diseases have increased. The epithelial lining of the airway forms the initial barrier; however, upon exposure, nanoplastics (NPs) may cross this interface and enter systemic circulation. This study aims to elucidate the effects of polypropylene nanoplastics (PP NPs) on the epithelial barrier and the interactions with serum proteins. PP beads were chemically degraded, characterized, and administered to the epithelial barrier‐on‐chip at a dose of 250 μg/mL, followed by continuous perfusion for 3 days. Their colloidal and biological behavior was investigated in cell culture medium supplemented with 10% fetal bovine serum. To explore clinical relevance, the interaction of PP NPs with human serum albumin was analyzed using molecular dynamics simulations, supported by protein profiling of plasma samples from healthy male and female individuals to understand gender‐related differences. PP NPs with an average size of 305 nm were exposed to the epithelial barrier‐on‐chip leading to a decrease in cell viability via apoptotic cell death and transepithelial electrical resistance (TEER) value from ~2600 to 2200 Ω·cm 2 with altered ZO‐1 and ACE2 expression, as well as an increased proinflammatory response and intracellular reactive oxygen species (ROS) levels. [Correction added on 15 April 2026, after first online publication: The word “suppressed” has been deleted from the abstract.] The size of NPs increased to 364 nm after incubation with cell culture medium, indicating protein corona formation. The simulation revealed a biphasic adsorption pattern. The major differences in blood plasma of male and female donors were observed in the protein bands around 130 and 180 kDa. By integrating experimental and computational approaches, this study advances our understanding of how inhaled NPs may interact with blood proteins upon systemic exposure, with potential implications for human health risk assessment.