Surface topography of nanoplastics modulates their internalization and toxicity in liver cells

Though hepatotoxicity induced by the ubiquitous and potentially ingested nanoplastics (NPs) has been extensively studied, limited attention has been given to the role of NPs' surface topography. Since these ingested NPs pass through the human digestive system (HDS) before reaching the liver, their surface properties are altered, which affects their interactions with the organ. Herein, we prepared two different-sized aggregation-induced emission fluorogen-incorporated NPs (AIE-NPs) with diverse surface roughness by exposing NPs to the HDS for different durations. The HDS environment could effectively alter the surface roughness of the AIE-NPs, leading to an extended specific surface area and decreased hydrophobicity. Besides, roughening the NPs' surface facilitated their cellular internalization efficiency, mainly mediated by the specific surface area, which has been confirmed in vivo in a zebrafish model. After internalization, all these investigated AIE-NPs were consistently localized in lysosomes (Pearson's correlation coefficient > 0.8), suggesting that the surface roughness had negligible influence on their intracellular distribution pattern. The AIE-NPs with the rougher surface contributed to lysosomal alkalization and potentially caused lysosomal autophagy. Furthermore, exposure to AIE-NPs triggered reactive oxygen species (ROS) production, mitochondrial glutathione (mGSH) depletion and mitochondria dysfunction. The roughest AIE-NPs displayed the strongest cytotoxicity and sequentially led to cell apoptosis. Overall, this study highlighted the critical role of NP nanoscale surface topography, strengthening the understanding and assessment of NP toxicology.

Automated summary

This study prepared aggregation-induced emission fluorogen-incorporated nanoparticles (AIE-NPs) with different surface roughness by exposing the nanoparticles to the human digestive system (HDS) for different durations. The study found that the surface roughness affected the interaction between the nanoparticles and the liver. Additionally, the rougher nanoparticles facilitated cellular internalization and induced lysosomal alkalization, ROS production, and cell apoptosis.