Transcriptomic investigation of NP toxicity on HepaRG spheroids

Area of Science:

• Nanomaterial toxicology
• Hepatocyte cell models

Background:

• Metal nanoparticles (NPs) are widely used, but their toxicity is a growing concern.
• Existing studies on NP toxicity are limited in scope regarding NP types, cell lines, and culture methods.
• Understanding NP adverse effects requires further investigation, particularly in liver models.

Purpose of the Study:

• To assess the impact of diverse metal NPs (varying materials and sizes) on HepaRG spheroids.
• To identify genes responding to acute NP toxicity in a liver spheroid model.
• To elucidate the toxicological mechanisms of NPs in HepaRG spheroids.

Main Methods:

• HepaRG cells cultured as 3D spheroids to mimic the liver microenvironment.
• Transcriptome analysis using RNA sequencing (RNA-seq) to identify differentially expressed genes (DEGs).
• Comparative analysis of DEGs across various NP types and sizes.

Main Results:

• Significant differences in DEGs observed, ranging from 118 for 40 nm AuNP to 1904 for InP/ZnS NPs.
• Enrichment of processes including drug metabolism, metal ion sensitivity, oxidative stress, endothelial-mesenchymal transition (EMT), and apoptosis across all NP types.
• Dysregulation of stress response pathways such as MAPK, p53, and mTOR upon NP exposure.

Conclusions:

• This study provides novel insights into NP toxicity mechanisms using a relevant liver spheroid model.
• Identified common and unique DEGs offer a basis for understanding NP-specific toxicological responses.
• The findings highlight the importance of considering NP material and size in toxicity assessments.