Key Laboratory of Environmental Medicine and Engineering, Ministry of Education; School of Public Health, & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University, Nanjing 210009, China; Jiangsu key Laboratory for Biomaterials and Devices, Southeast University, Nanjing 210009, China.
Key Laboratory of Environmental Medicine and Engineering, Ministry of Education; School of Public Health, & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University, Nanjing 210009, China; Jiangsu key Laboratory for Biomaterials and Devices, Southeast University, Nanjing 210009, China.
Toxicol In Vitro. 2018 Oct;52:41-51. doi: 10.1016/j.tiv.2018.05.014. Epub 2018 May 28.
The excellent optical properties of CdTe quantum dots (QDs) make researchers realize their value on the application of biomedicine, especially neuroscience, as an advanced fluorescent probe. Thus, it is important to evaluate the biosafety of CdTe QDs on the central nervous system (CNS). Our previous studies have conducted a systematic biosafety evaluation of CdTe QDs on the CNS and found several toxic endpoints, one of which is the inflammation on the rat hippocampus, but their underlying mechanism remains unclear. In this study, when BV2 microglial cells were exposed to CdTe QDs with doses <20 nM, there was no obviously adverse effect. However, 40 nM CdTe QDs exposure could significantly activate the BV2 cells and increase the pro-inflammatory cytokine IL-1ß secretion. Molecular biology analyses suggested that both TLR2/MyD88/NF-κB pathway and NLRP3 inflammasome participated in the CdTe QD-induced IL-1ß secretion. The former served as the first signal for pro-IL-1ß expression, while the later played a role on the maturation of pro-IL-1ß into IL-1ß. The results, taken together, demonstrated that MPA-modified CdTe QDs exposure with a high concentration was capable of activating microglial cells and promoting IL-1ß secretion, which was highly correlated with the activations of both TLR2/MyD88/NF-κB pathway and ROS-induced NLRP3 inflammasome. These findings provide some mechanistic insights regarding the neuroinflammatory responses to cadmium-based QDs.
碲化镉量子点（QDs）具有优异的光学性能，这使得研究人员意识到它们在生物医药领域的应用价值，尤其是在神经科学领域，可用作先进的荧光探针。因此，评估碲化镉量子点在中枢神经系统（CNS）中的生物安全性非常重要。我们之前的研究已经对 CNS 中的碲化镉量子点进行了系统的生物安全性评估，发现了几个毒性终点，其中之一是大鼠海马体的炎症，但它们的潜在机制尚不清楚。在这项研究中，当 BV2 小胶质细胞暴露于低于 20nm 的剂量的碲化镉量子点时，没有明显的不良影响。然而，40nm 的碲化镉量子点暴露可显著激活 BV2 细胞并增加促炎细胞因子 IL-1ß 的分泌。分子生物学分析表明，TLR2/MyD88/NF-κB 途径和 NLRP3 炎性小体都参与了 CdTe QD 诱导的 IL-1ß 分泌。前者作为 pro-IL-1ß 表达的第一信号，而后者在 pro-IL-1ß 成熟为 IL-1ß 中发挥作用。总的来说，这些结果表明，高浓度 MPA 修饰的 CdTe QDs 暴露能够激活小胶质细胞并促进 IL-1ß 的分泌，这与 TLR2/MyD88/NF-κB 途径和 ROS 诱导的 NLRP3 炎性小体的激活密切相关。这些发现为基于镉的 QDs 的神经炎症反应提供了一些机制上的见解。
