SiO

Summary

Using human midbrain organoids, silica nanoparticles disrupted dopaminergic lineage maturation by reducing progenitor proliferation and dopaminergic markers without inducing apoptosis. The mechanism involved suppressed intracellular ROS, impaired calcium signaling, and astrocytic/inflammatory pathway activation, revealing a non-cytotoxic, redox-suppressed developmental neurotoxicity.

Key Findings

• SiO2-NP exposure reduced organoid growth and neural progenitor proliferation and downregulated dopaminergic markers without inducing apoptosis.
• Intracellular ROS levels were diminished and calcium signaling was impaired, alongside activation of astrocytic and inflammatory pathways.
• Phospho-kinase profiling and RNA-seq revealed suppression of calcium- and redox-dependent signaling networks with metabolic/inflammatory reprogramming.
• Overall neuronal populations were preserved despite dopaminergic lineage disruption, indicating a non-cytotoxic, developmental mechanism.

Clinical Implications

Encourages incorporation of human organoid assays into cosmetic ingredient safety testing, reconsideration of nanoparticle size/coatings, and precautionary measures for pregnant users until exposure–response data are clarified.

Limitations

• In vitro organoid model lacks maternal–fetal toxicokinetics and immune/endocrine interactions
• Exposure levels and realistic consumer-use scenarios were not directly bridged

Future Directions

Establish exposure–response bridging to consumer-relevant doses, validate findings in complementary in vivo models, and assess particle size/coating modifications to mitigate risk.