Nanoplastics Enhance Transmembrane Transport of Carcinogens and Induce Cellular Stress Responses as Revealed by mRNA Sequencing Analysis
Nanoplastics were generated from common consumer plastics (PET, HDPE, PS, PVC) and exposed to simulated marine weathering for up to 10 weeks. Fourier-Transform Infrared (FT-IR) spectroscopy and ?-potentials measurements revealed continuous changes in the composition of the nanoplastics consistent with oxidation. Although the chemical composition and oxidation of the nanoplastics influenced their ability to sorb Polycyclic Aromatic Hydrocarbons (PAHs), for all investigated conditions, sorption of PAH to nanoplastics achieved effective PAH concentrations that were orders of magnitude higher than the solubility limit in water. In an intestinal membrane model, PAH-loaded nanoplastics enhanced 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 revealed significant transcriptional changes, including upregulation of oxidative stress and detoxification pathways (NQO1, CYP1A1, CYP1B), especially in response to PAH-loaded nanoplastics, while genes associated with basic cell functions, such as cellular migration (NCKAP5, MACROD2) and division (KIF20A) were downregulated. These findings suggest that nanoplastics can increase bioaccessibility and bioavailability of hydrophobic carcinogens and enhance cellular stress, raising concerns about the potential environmental and health impacts associated with nanoplastics as carriers of hydrophobic environmental toxins. Overall design: Cells were exposed to PET, PVC, HDPE, or PS with no weathering (native), 4 weeks or 10 weeks of weathering. All nanoplastics conditions were considered with and without PAH loading and for an exposure duration of 24 h. We also included cells exposed to free PAHs at their respective solubility limit in water (WaterPAH, 3 biological replicates) and untreated membranes as no treatment controls (NoTreat, 4 biological replicates)