Quantum dots (QDs) were reported to be metabolized by the liver and demonstrated to be toxic in vitro and in vivo with unclear mechanisms, which largely limited their applications in the field of biomedical research. To improve their biosafety, the mechanism of how the QDs triggered hepatotoxicity was evaluated in this study. We found that CdTe/CdS QDs can trigger significant apoptosis-independent nanotoxicity after their uptake by liver cells and internalization into lysosomes. Besides, the lysosomal enzymes were abnormally activated after the QDs entered the lysosomes, which caused reactive oxygen species (ROS) production and autophagy activation. Importantly, inhibition of lysosomal enzymes not only rescued the viability of liver cells but also blocked the production of ROS and activation of autophagic flux, whereas inhibition of ROS and autophagy could ameliorate the hepatotoxicity induced by QDs but had no impact on the activity of lysosomal enzymes. Our results elucidate the relationship among the lysosomes, ROS, and autophagy in QDs-induced hepatotoxicity, which indicate that the QDs can elicit hepatotoxicity through lysosome-dependent autophagy activation and ROS production, highlighting an approach to improve the biosafety of QDs by lysosomal inhibition.
Keywords: ROS; autophagy; lysosome; nanotoxicity; quantum dots.