Intranasal Zinc Oxide Nanoparticles Induce Neuronal PANoptosis via Microglial Pathway.

Summary

Intranasal zinc oxide nanoparticles entered the brain via the nose-to-brain route, accumulated in microglia, and triggered microglia-derived NOX2-ROS, leading to neuronal PANoptosis. These mechanistic insights link inhalable nanoparticle exposure to neurotoxicity relevant to consumer products and occupational settings.

Key Findings

• Intranasal ZnO nanoparticles entered the brain via the nose-to-brain pathway and accumulated in microglia, not astrocytes or neurons.
• Microglia-derived oxidative stress via NOX2-generated ROS led to neuronal membrane lipid peroxidation and Ca2+ increase.
• Neuronal PANoptosis was induced in co-culture, linking microglial activation to integrated cell death pathways.

Clinical Implications

Caution is warranted for aerosolized or inhalable nanoparticle formulations (e.g., sprays, powders) in cosmetic and consumer products, and for occupational exposures. Safety evaluations should incorporate nose-to-brain transport, microglial accumulation, and NOX2-mediated pathways.

Limitations

• Preclinical study; human dose-response and exposure relevance remain uncertain.
• Focus on intranasal route may not generalize to dermal-only cosmetic exposures.

Future Directions

Quantitative dose-response and chronic exposure studies in relevant animal models and humans; evaluation of coated vs uncoated ZnO and alternative formulations; exploration of NOX2 inhibition as a protective strategy.