Nanoplastics Enhance Transmembrane Transport and Uptake of Carcinogens: Transcriptional Changes and the Effects of Weathering

AbstractNanoplastics are generated from common consumer plastics (polyethylene terephthalate, high‐density polyethylene, polystyrene, polyvinyl chloride) and exposed to simulated marine weathering for up to 10 weeks. Fourier‐transform infrared spectroscopy and ζ‐potential measurements reveal continuous changes in the composition of the nanoplastics, consistent with oxidation. Although the chemical composition and oxidation of the nanoplastics influence their ability to sorb polycyclic aromatic hydrocarbons (PAHs), for all investigated conditions, sorption of PAHs to nanoplastics achieves effective PAH concentrations that are orders of magnitude higher than the solubility limit in water. In an intestinal co‐culture model membrane consisting of M cells and enterocytes, PAH‐loaded nanoplastics enhance the overall PAH transport into and across the membrane, with HDPE achieving the highest intracellular PAH concentration. RNA sequencing of cell membranes exposed to nanoplastics reveals significant transcriptional changes, including upregulation of oxidative stress and detoxification pathways (NQO1, CYP1A1, CYP1B1), especially in response to PAH‐loaded nanoplastics, while genes associated with basic cell functions, such as DNA repair (MACROD2) and division (KIF20A), are downregulated. These findings confirm the feasibility of nanoplastics to increase bioaccessibility and bioavailability of hydrophobic carcinogens and enhance cellular stress, which underscores the potential environmental and health impacts associated with nanoplastics as carriers of hydrophobic environmental toxins.