Background: The detection of nanoplastics (NPs) in food, water, and air has intensified global concern regarding their environmental and health impacts 1,2. Human exposure occurs unintentionally through ingestion, inhalation, or skin contact, raising questions about their interactions with biological systems, especially the nervous system 3–5. Although accumulating data confirms the biological activity of NPs, the pathways underlying their neurotoxic potential — especially those shaped by surface functionalization — are still largely unresolved. Objective: This study investigates the neurotoxic effects of four polystyrene nanoplastics (PS-NPs): unmodified 50 and 100 nm PS-NPs and 100 nm amine- and carboxyl-functionalized PS-NPs, using the human SH-SY5Y neuronal cell line. Methods: SH-SY5Y cells were incubated with varying NP concentrations (1–500 µg/mL) for 24 or 48 hours. Before initiating cytotoxicity assays, the physicochemical features and medium stability of the particles were verified. The analysis focused on metabolic activity, ROS/RNS generation, nanoparticle uptake, and cellular or subcellular structural alterations. Results: Functionalized PS-NPs, notably amine-modified particles, induced higher toxicity than non-functionalized ones. Cell viability declined in a concentration- and time-dependent manner, with significant reductions observed at 200–500 µg/mL. Elevated ROS/RNS levels occurred for plain 100 nm and amine-functionalized NPs, with oxidative stress intensifying over time. Electron microscopy revealed marked subcellular damage — endoplasmic reticulum dilation, mitochondrial impairment, and Golgi disorganization — correlated with NP size, concentration, and surface chemistry. Surface-modified NPs exhibited enhanced internalization efficiency, with amine-functionalized variants demonstrating the highest accumulation within neuronal cells. Mechanistic analyses indicated activation of apoptosis, autophagy, and lysosomal dysfunction, strongest in cells exposed to functionalized PS-NPs. Conclusions: NP surface functionalization critically influences neurotoxicity, raising significant concerns about the long-term impact of NP exposure and its potential involvement in neurodegenerative disease processes.
Mota et al. (Fri,) studied this question.