Functionalized polystyrene nanoplastics induce distinct toxicity and transcriptomic changes in human intestinal Caco-2 cells

The plastic waste can be progressively disintegrated into microscale (MPs; 1 μm-5 mm) and nanoscale particles (NPs; 1 nm–1 μm) through the long-term influence of mechanical forces of water, ultraviolet radiation, and biological degradation. Humans are mainly exposed to MPs and NPs through oral intake. Following their ingestion, particles can penetrate intestinal mucosa, be transported to reach the circulatory system, and deposit in various organs, posing a serious risk to health. Polystyrene (PS) is an important thermoplastic found in disposable drinking cups, packaging, and personal care products. In the present study, unmodified PS or differently functionalized NPs (PS-COOH and PS-NH2; 100 nm in size) were selected as experimental models and administered to colorectal adenocarcinoma Caco-2 cells, as a model of intestinal epithelia cells potentially highly exposed to microplastics. A comparison of internalization process into cells among differently functionalized NPs was performed by confocal microscopy and cytofluorimetric analysis. Fluorescent PS-COOH and PS-NH2 NPs were detected to interact with cells after 2 h-incubation, and they continued to accumulate within 24 h. PS-NH2 significantly reduced cell viability in a dose and time dependent way, while treatments with PS and PS-COOH were well tolerated and only the highest concentrations of PS-COOH were able to decrease cell viability after 96 h. From transcriptome sequence analysis 125 genes were differentially expressed by PS-NH2 treatment for 24 h. Some genes were related to inflammation, apoptosis, and oxidative stress, and were involved in the Wnt signalling pathway. This study provides transcriptomic-level insights into the cellular responses of Caco-2 cells to PS nanoplastics, highlighting differentially expressed genes and pathways potentially associated with cytotoxicity.