Polystyrene nanoparticles and death of erythrocytes: does exposure induce eryptosis?

Abstract

The widespread presence of polystyrene nanoparticles (PS-NPs) in the human body has raised concerns about their potential biological toxicity. When assessing the safety of nanoparticles and other xenobiotics, a key aspect is their effect on blood cells, particularly erythrocytes, which experience the most direct exposure to nanoparticles circulating in the bloodstream. The present study evaluated the impact of non-functionalized PS-NPs with diameters of ∼30 nm, ∼45 nm, and ∼70 nm on human red blood cells after 24 hours of incubation. The studied PS-NPs did not influence intracellular Ca²⁺ ion levels or caspase 3 activity, and did not induce phosphatidylserine translocation at pre-hemolytic concentrations (below 100 µg/mL). Moreover, exposure did not increase intracellular ROS levels at any of the tested concentrations, suggesting that generalized intracellular oxidative stress is likely not the primary mechanism underlying the effects induced by PS-NPs in human erythrocytes. However, the observed increase in lipid peroxidation, detected from 50 µg/ml, indicates that oxidative damage at the membrane level may contribute to the overall toxic response. The results suggest that PS-NPs interact primarily with the erythrocyte membrane, leading to membrane destabilization associated with increased calpain activity, observed already at a concentration of 1 µg/mL, and enhanced lipid peroxidation. It is noteworthy that the most pronounced changes were induced by the smallest nanoparticles (∼30 nm), suggesting a size-dependent effect on erythrocyte integrity. These findings suggest that PS-NP toxicity in erythrocytes is mediated mainly through red blood cell membrane destabilization rather than classical intracellular oxidative stress alone.