Polystyrene nanoplastics-induced methuosis in brain microvascular endothelial cells: Rescue via ESCRT membrane repair system

Nanoplastic pollution has emerged as a significant environmental concern, with increasing evidence suggesting that these nanoparticles can disrupt the blood-brain barrier (BBB) and accumulate in the brain, ultimately leading to neurological impairment. However, the underlying mechanism for the toxic effects of nanoplastics on the BBB remain poorly understood. In this study, we explored the toxic effects of polystyrene nanoplastic (PSNP) on brain microvascular endothelial cells (BMECs), one of the most critical components for maintaining BBB integrity. Our results revealed that PSNP specifically accumulate in the endolysosomal system following their internalization by BMECs. This accumulation disrupts lysosomal function and blocks endolysosomal pathways, ultimately triggering methuosis-a unique form of cell death characterized by extensive cytoplasmic vacuolization. Although the endosomal sorting complexes required for transport (ESCRT) system is naturally activated as a cellular defense mechanism, it is insufficient to repair PSNP-induced lysosomal membrane damage. By enhancing ESCRT activity, we effectively restored lysosomal function, thereby preventing cellular methuosis and preserving BBB integrity. Therefore, our findings provide crucial insights into the mechanisms underlying PSNP-induced BBB disruption by focusing on methuosis in endothelial cells. These insights hold important implications for environmental toxicology and public health in the context of global plastic pollution.