The transport and fate of nanoplastics through the blood brain barrier: the role of intracellular localization

Nanoplastics (NPs), synthetic polymers ranging from 1 nm to 1 μm, are widely detected in the environment and the food chain, raising concerns about their potential health risks. Indeed, they may cause health problems like inflammation and immune system disruptions following exposure via different routes such as inhalation or ingestion. Critically, once inside human body, the interactions between nanoplastics and biological molecules, such as proteins, can significantly influence their cellular uptake and subsequent behavior. The formation of a "protein corona" around NPs due to adsorption of proteins from body fluids has been shown to affect their characteristics and properties. This places particular emphasis on the understanding of the mechanisms and pathways involved in their accumulation and translocation within the human body, being directly related to their fate and persistence within organs and tissues. This study investigates the capability of 100 nm carboxylated polystyrene nanoparticles, used as a nanoplastic model, to cross the human brain endothelial hCMEC/D3 cell layer and be internalized by human brain tumor U87 cells, focusing on the role of intracellular localization. We compared NPs confined in the endo-lysosomal compartment, delivered through endocytosis, with free NPs in the cytoplasm, delivered by the gene gun method. The results indicate that the intracellular behavior of NPs changed as a function of their entrance mechanism. Notably, by bypassing endo-lysosomal accumulation, free NPs were released from cells more efficiently than endocytosed NPs. Furthermore, once excreted by the endothelial cells, free NPs were released as smaller aggregates compared to endocytosed NPs, and consequently, they entered the human glioblastoma U87 cells more efficiently. These findings demonstrate that the intracellular localization of nanoplastics can significantly impact their long-term fate, including their cellular release and subsequent cellular uptake in the brain parenchyma. The study opens new questions about their potential long-term effects on human health, the biological mechanisms underlying their excretion and the evolution of the protein corona around NPs that experience different intracellular environments. The insights gained from this research contribute to a better understanding of the fate and behavior of nanoplastics in the brain, which is crucial for assessing their potential toxicological implications.