Abstract

The increasing prevalence of micro- and nanoplastics (MNPLs) in the environment necessitates a detailed examination of their potential health impacts and the factors influencing these responses. Since internalization is a prerequisite for inducing adverse effects, we investigated the roles of surface modifications and polymer composition in human liver cells (HUH-7). Our study compared the internalization and effects of a pristine polystyrene nanoplastic (PS50-NPLs), two carboxylated polystyrenes of different sizes (cPS50-NPLs and cPS100-NPLs), and two environmentally relevant nanoplastics derived from polyethylene terephthalate water bottles (PET-NPLs) and polylactic acid pellets (PLA-NPLs). Significant variations in cell internalization were observed, with cPS50-NPLs and PET-NPLs showing the highest levels, and PS50-NPLs showing the lowest. Interestingly, internalization alone did not correlate directly with the induced effects; only PET-NPLs and PLA-NPLs induced reactive oxygen species (ROS), genotoxicity, and increased cytokine release. These results suggest that while internalization is essential in assessing MNPL toxicity, harmful effects also depend on other particle characteristics. The notable impact of the realistic environmental models PET-NPLs and PLA-NPLs underscores the importance of using environmentally representative MNPLs to better assess the health risks associated with environmental MNPL exposure. This journal is © The Royal Society of Chemistry, 2025