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Previous studies have revealed that the liver is the main target organ of deposition for engineered nanoparticles. The hepatotoxicity of silver nanoparticles (AgNPs), the widely used antimicrobial nanoparticles, has been of great interest. However, little is known about the regulatory mechanism of the mitochondria in AgNP-induced hepatotoxicity. In the present study, we found that AgNPs, rather than silver ions, induced mitochondrial dynamics disorders, oxidative stress, and mitochondria-dependent hepatocyte apoptosis in mice. Using human hepatocellular carcinoma (HepG2) cells, we confirmed that the interaction between dynamin-related protein 1 (DRP1)-dependent mitochondrial fission and oxidative stress promoted mitochondrial damage and mitochondria-dependent apoptosis induced by AgNPs, as determined by the elimination of DRP1 or addition of N-acetylcysteine (NAC). Interestingly, the crosstalk between DRP1-dependent mitochondrial fission and oxidative stress also activated mitophagy and autophagy flux blocking. Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) gene silencing contributed to the aggravation of mitochondrial damage, oxidative stress, and apoptosis. These results revealed that the interplay between mitochondrial fission and oxidative stress induced mitophagy defects and triggered AgNP-induced mitochondria-dependent apoptosis in liver cells both in vivo and in vitro. Our findings provide a perspective for the mechanism of hepatotoxicity induced by exposure to metal NPs.

Silver selenide quantum dots (Ag2Se QDs) provide bright prospects for the application of QDs in the field of biomedicine because they contain low-toxic compounds and show great advantages in the imaging of deep tissues and tiny vascular structures. However, the biosafety of these novel QDs has not been thoroughly evaluated, especially in one main target for toxicity-the central nervous system (CNS). Our previous studies have suggested severe inflammatory responses to cadmium-containing QDs in the hippocampus, which gives us a hint regarding the risk assessment of Ag2Se QDs. In this study, microglial activation followed by enhanced levels of pro-inflammatory cytokines was observed in the hippocampus of mice intravenously injected with Ag2Se QDs. When using the microglial BV2 cells to investigate the underlying mechanisms, we found that the NLRP3 inflammasome activation was involved in the IL-1β-mediated inflammation induced by Ag2Se QDs. On the one hand, Ag2Se QD-activated NF-κB participated in the NLRP3 inflammasome priming and assembly as well as the pro-IL-1β upregulation. On the other hand, Ag2Se QD-induced ROS generation, particularly mtROS, triggered the NLRP3 inflammasome activation and resulted in active caspase-1 to process pro-IL-1β into mature IL-1β release. These findings not only indicated that it is important to evaluate the biosafety of novel QDs, even those containing low-toxic compounds, but also provided an unbiased and mechanism-based risk assessment of similar nanoparticles.

Silver selenide quantum dots (Ag

As quantum dots (QDs) are widely used in biomedical applications, the number of studies focusing on their biological properties is increasing. While several studies have attempted to evaluate the toxicity of QDs towards neural cells, the in vivo toxic effects on the nervous system and the molecular mechanisms are unclear. The aim of the present study was to investigate the neurotoxic effects and the underlying mechanisms of water-soluble cadmium telluride (CdTe) QDs capped with 3-mercaptopropionic acid (MPA) in Caenorhabditis elegans (C. elegans). Our results showed that exposure to MPA-capped CdTe QDs induced behavioral defects, including alterations to body bending, head thrashing, pharyngeal pumping and defecation intervals, as well as impaired learning and memory behavior plasticity, based on chemotaxis or thermotaxis, in a dose-, time- and size-dependent manner. Further investigations suggested that MPA-capped CdTe QDs exposure inhibited the transporters and receptors of glutamate, serotonin and dopamine in C. elegans at the genetic level within 24 h, while opposite results were observed after 72 h. Additionally, excessive reactive oxygen species (ROS) generation was observed in the CdTe QD-treated worms, which confirmed the common nanotoxicity mechanism of oxidative stress damage, and might overcome the increased gene expression of neurotransmitter transporters and receptors in C. elegans induced by long-term QD exposure, resulting in more severe behavioral impairments.