The surface charge both influences the penetration and safety of polystyrene nanoparticles despite the protein corona formation

Micro- and nano-plastics' (MNPs') environmental persistence generates relevant alarm. This concern is amplified for non-biodegradable materials like polystyrene (PS). It is known that MNPs easily penetrate cells and accumulate in vital organs. Despite the great interest, a univocal idea about MNPs' toxicity is still lacking. In this study, PS-nanoparticles (PS-NPs) were employed as prototypic material. We focused our attention on the role played by the external surface in the internalization and toxicity of amine- and carboxylate-modified fluorescent PS-NPs with different z-potentials. Human embryonic kidney (HEK) 293 cells and C. elegans have been employed to model the effects of PS-NPs in vitro and in vivo. Both positive and negative PS-NPs entered cells primarily by clathrin-mediated endocytosis and were rapidly trapped by lysosomes. However, amine-modified positive NPs were more uptaken than negative ones and caused a dose-dependent decrease in cell growth and viability in HEK 293 cells. Internalized NPs and their mean distance from the cell nucleus have also been quantitatively characterized through a dedicated Cell Profiler-Matlab pipeline. The z-potential of PS-NPs also affected their toxic effect in vivo, being only positive NPs able to cause a dose-related decrease of C. elegans viability and defects in motility, pharyngeal function, reproduction, and development. These results underline the crucial role of the surface charge of PS-NPs in their interaction with cell membranes and in vitro and in vivo biological effects.