Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China.
Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China; Jiaxing Center for Disease Control and Prevention, Jiaxing, 314050, China.
NanoImpact. 2022 Jan;25:100392. doi: 10.1016/j.impact.2022.100392. Epub 2022 Feb 16.
Quantum dots (QDs), also known as semiconductor QDs, have specific photoelectricproperties which find application in bioimaging, solar cells, and light-emitting diodes (LEDs). However, the application of QDs is often limited by issues related to health risks and potential toxicity. The purpose of this study was to provide evidence regarding the safety of cadmium telluride (CdTe) QDs by exploring the detailed mechanisms involved in its hepatotoxicity. This study showed that CdTe QDs can increase reactive oxygen species (ROS) in hepatocytes after being taken up by hepatocytes, which triggers a significant mitochondrial-dependent apoptotic pathway, leading to hepatocyte apoptosis. CdTe QDs-induce mitochondrial cristae abnormality, adenosine triphosphate (ATP) depletion, and mitochondrial membrane potential (MMP) depolarization. Meanwhile, CdTe QDs can change the morphology, function, and quantity of mitochondria by reducing fission and intimal fusion. Importantly, inhibition of ROS not only protects hepatocyte viability but can also interfere with apoptosis and activation of mitochondrial dysfunction. Similarly, the exposure of CdTe QDs in Institute of Cancer Research (ICR) mice showed that CdTe QDs caused oxidative damage and apoptosis in liver tissue. NAC could effectively remove excess ROS could reduce the level of oxidative stress and significantly alleviate CdTe QDs-induced hepatotoxicity in vivo. CdTe QDs-induced hepatotoxicity may originate from the generation of intracellular ROS, leading to mitochondrial dysfunction and apoptosis, which was potentially regulated by mitochondrial dynamics. This study revealed the nanobiological effects of CdTe QDs and the intricate mechanisms involved in its toxicity at the tissue, cell, and subcellular levels and provides information for narrowing the gap between in vitro and in vivo animal studies and a safety assessment of QDs.
量子点（Quantum dots，QDs），也称为半导体量子点，具有特定的光电特性，在生物成像、太阳能电池和发光二极管（Light-Emitting Diodes，LEDs）等领域有应用。然而，QDs 的应用常常受到与健康风险和潜在毒性相关的问题的限制。本研究旨在通过探讨 CdTe QDs 肝毒性的详细机制，为 CdTe QDs 的安全性提供证据。本研究表明，CdTe QDs 被肝细胞摄取后会在肝细胞内增加活性氧（Reactive Oxygen Species，ROS），从而触发显著的线粒体依赖性凋亡途径，导致肝细胞凋亡。CdTe QDs 诱导的线粒体嵴异常、三磷酸腺苷（Adenosine Triphosphate，ATP）耗竭和线粒体膜电位（Mitochondrial Membrane Potential，MMP）去极化。同时，CdTe QDs 通过减少分裂和内膜融合来改变线粒体的形态、功能和数量。重要的是，抑制 ROS 不仅可以保护肝细胞活力，还可以干扰凋亡和线粒体功能障碍的激活。同样，在 Institute of Cancer Research（ICR）小鼠中暴露于 CdTe QDs 表明，CdTe QDs 导致肝脏组织氧化损伤和细胞凋亡。NAC 可以有效地去除过多的 ROS，降低氧化应激水平，并显著缓解体内 CdTe QDs 诱导的肝毒性。CdTe QDs 诱导的肝毒性可能源于细胞内 ROS 的产生，导致线粒体功能障碍和凋亡，这可能受到线粒体动力学的调节。本研究揭示了 CdTe QDs 的纳米生物学效应及其在组织、细胞和亚细胞水平上的毒性的复杂机制，为缩小体外和体内动物研究之间的差距以及 QDs 的安全性评估提供了信息。
