Long-term low-dose exposure to polystyrene nanoplastics induces morphological and transcriptional reprogramming to enhance metastatic potential of colorectal cancer cells

Despite global efforts to reduce plastic consumption, its usage continues to rise, leading to increased environmental contamination and heightened concerns regarding the potential health impacts of nanoplastics. Owing to their prolonged residence time in the intestine, nanoplastics contribute to prolonged exposure and absorption by intestinal epithelial cells. In this study, we examined the effects of polystyrene micro- and nanoplastics of varying sizes (20 nm-1000 nm) on colorectal cancer cells (HCT116) through a series of in vitro experiments, including cell viability assays, morphological assessments, and transcriptomic profiling. Notably, long-term exposure of HCT116 cells to small-sized (20 nm) nanoplastics at a low-dose, one that does not cause acute toxicity, led to significant morphological changes and gene expression alterations. These modifications included the upregulation of markers associated with migration, cancer stem cell (CSC) properties, and epithelial-mesenchymal transition (EMT). The enhanced expression of migration markers correlated with increased cell motility. Consistent with these in vitro findings, zebrafish models demonstrated accelerated metastasis of colorectal cancer cells following nanoplastic exposure. Collectively, these results suggest that nanoplastics may contribute to colorectal cancer progression, providing new insights into the molecular mechanisms underlying this process.