Integrin A5B1-mediated endocytosis of polystyrene nanoplastics: Implications for human lung disease and therapeutic targets

The extensive use of plastic products has exacerbated micro/nanoplastic (MPs/NPs) pollution in the atmosphere, increasing the incidence of respiratory diseases and lung cancer. This study investigates the uptake and cytotoxicity mechanisms of polystyrene (PS) NPs in human lung epithelial cells. Transcriptional analysis revealed significant changes in cell adhesion pathways following PS-NPs exposure. Integrin α5β1-mediated endocytosis was identified as a key promoter of PS-NPs entry into lung epithelial cells. Overexpression of integrin α5β1 enhanced PS-NPs internalization, exacerbating mitochondrial Ca2+ dysfunction and depolarization, which induced reactive oxygen species (ROS) production. Mitochondrial dysfunction triggered by PS-NPs led to oxidative damage, inflammation, DNA damage, and necrosis, contributing to lung diseases. This study elucidates the molecular mechanism by which integrin α5β1 facilitates PS-NPs internalization and enhances its cytotoxicity, offering new insights into potential therapeutic targets for microplastic-induced lung diseases. [Display omitted] •Primary Pathway for Nanoplastic Entry: Integrin A5B1 is key for nanoplastic internalization into lung epithelial cells, representing a novel discovery in nanoplastic entry pathways.•Consequences of Integrin A5B1 Overexpression: Increased Integrin A5B1 expression enhances nanoplastic uptake and elevates reactive oxygen species (ROS) production, indicating potential cellular risks.•Cellular Impact of Elevated ROS: Elevated ROS from enhanced nanoplastic entry via Integrin A5B1 leads to significant mitochondrial depolarization, extensive DNA damage, and increased necrosis.