Plastic nanoparticles interfere with extracellular vesicle pathway in primary astrocytes

Area of Science:

• Environmental Toxicology
• Cell Biology
• Nanotechnology

Background:

• Plastic microparticles (MPs) and nanoparticles (NPs) contribute to environmental pollution and pose health risks.
• Nanoparticle toxicity mechanisms, including oxidative stress and cell death, require further investigation.
• Astrocytes play crucial roles in brain function and are potential targets for nanoparticle toxicity.

Purpose of the Study:

• To investigate the internalization and intracellular fate of polystyrene nanoparticles (PS-NPs) in primary astrocytes.
• To determine if PS-NPs interfere with intercellular communication mediated by extracellular vesicles (EVs).
• To analyze the impact of PS-NPs on the protein cargo of EVs released by astrocytes.

Main Methods:

• Primary astrocyte cultures were exposed to fluorescent PS-NPs at varying concentrations and time points.
• Electron microscopy and confocal imaging were used to track PS-NP internalization and localization.
• Proteomic analysis was performed on extracellular vesicles (EVs) released by exposed astrocytes.

Main Results:

• PS-NPs were internalized by astrocytes and accumulated in the cytoplasm within the endosomal-lysosomal system in a concentration-dependent manner.
• Astrocytes exposed to PS-NPs released EVs containing encapsulated PS-NPs, facilitating intercellular transfer.
• PS-NPs altered the protein composition of released EVs, decreasing levels of CD47, CSTB, and CNDP2.

Conclusions:

• Intercellular transport of PS-NPs in astrocytes is mediated by EVs.
• EV-mediated release of PS-NPs may modulate toxicity in individual cells but can spread effects to neighboring cells.
• PS-NP exposure disrupts protein sorting in EVs, potentially impairing astrocyte-mediated cell-cell communication.