Impact of a pristine versus gastric acid-treated low-density polyethylene in a human epithelial colorectal adenocarcinoma (Caco-2) cell line

An increasing number of studies report the presence and accumulation of micro- and nanoplastics (MNPs) in the human body. After ingestion, MNPs undergo weathering by gastric and intestinal fluids that modify their physicochemical properties. Although these changes can influence biological responses, their impact remains understudied, forming the foundation of this research. We investigated how a simplified chemical weathering model of simulated gastric fluid exposure alters the physicochemical properties of environmentally relevant microplastics and how these changes influence their subsequent effects on a human epithelial colorectal adenocarcinoma (Caco-2) cell line. We focused on Low-Density Polyethylene (LDPE) due to its widespread use in agriculture and food packaging, as well as its status as one of the most widely produced plastic polymers. Particle properties changed after artificial stomach acid (ASA) treatment, including metal leaching, surface modifications, stronger redox-inducing potential, and increased floatability. These changes in the particles' characteristics were reflected in the observed effects, with ASA-treated particles producing more pronounced alterations in mitochondrial network features, including increased mitochondrial fusion and a larger mitochondrial footprint. No internalization was observed in any of the cases, with membrane integrity (5-CFDA,AM) disrupted after exposure to pristine and ASA-treated particles, regardless of the underlying mechanistic pathways. In summary, our findings show that ASA-treated microplastics differ in redox-inducing potential, which can influence cellular metabolism regardless of cellular uptake. This suggests that indirect changes after ASA treatment may represent an underestimated part of microplastic toxicity after ingestion.