Department of Biomedical Engineering, Key Laboratory of Biomedical Engineering of Ministry of Education, Zhejiang University, Zheda Road 38, Hangzhou 310027, China.
Toxicology. 2011 Apr 11;282(3):94-103. doi: 10.1016/j.tox.2011.01.015. Epub 2011 Feb 1.
Quantum dots (QDs), as novel bioimaging and drug delivery agents, are generally introduced into vascular system by injection, and thus directly exposed to vascular endothelial cells (ECs). However, the adverse effects of QDs on ECs are poorly understood. In this study, employing human umbilical vein ECs (HUVECs), we investigated the potential vascular endothelial toxicity of mercaptosuccinic acid (MSA)-capped CdTe QDs in vitro. In the experiment, water-soluble and pH stable CdTe QDs were synthesized; and the cell viability assays showed that CdTe QDs (0.1-100μg/mL) dose-dependently decreased the cell viability of HUVECs, indicating CdTe QDs induced significant endothelial toxicity. The flow cytometric and immunofluorescence results revealed that 10μg/mL CdTe QDs elicited significant oxidative stress, mitochondrial network fragmentation as well as disruption of mitochondrial membrane potential (Δψ(m)); whereas ROS scavenger could protect HUVECs from QDs-induced mitochondrial dysfunction. Moreover, upon 24h exposure to 10μg/mL CdTe QDs, the apoptotic HUVECs dramatically increased by 402.01%, accompanied with alternative expression of apoptosis proteins, which were upregulation of Bax, downregulation of Bcl-2, release of mitochondrial cytochrome c and cleavage of caspase-9/caspase-3. These results suggested that CdTe QDs could not only impair mitochondria but also exert endothelial toxicity through activation of mitochondrial death pathway and induction of endothelial apoptosis. Our results provide strong evidences of the direct toxic effects of QDs on human vascular ECs, and reveal that exposure to QDs is a significant risk for the development of cardiovascular diseases. These results also provide helpful guidance on the future safe use and manipulation of QDs to make them more suitable tools in nanomedicine.
量子点（QDs）作为新型的生物成像和药物传递剂，通常通过注射引入血管系统，因此直接暴露于血管内皮细胞（ECs）。然而，QDs 对 ECs 的不良影响知之甚少。在这项研究中，我们用人脐静脉内皮细胞（HUVECs）研究了巯基琥珀酸（MSA）封端的 CdTe QDs 在体外的潜在血管内皮毒性。在实验中，合成了水溶性和 pH 稳定的 CdTe QDs；细胞活力测定表明，CdTe QDs（0.1-100μg/mL）剂量依赖性地降低了 HUVECs 的细胞活力，表明 CdTe QDs 诱导了显著的内皮毒性。流式细胞术和免疫荧光结果表明，10μg/mL CdTe QDs 引起了明显的氧化应激、线粒体网络碎片化以及线粒体膜电位（Δψ（m））的破坏；而 ROS 清除剂可以保护 HUVECs 免受 QDs 诱导的线粒体功能障碍。此外，在暴露于 10μg/mL CdTe QDs 24 小时后，凋亡的 HUVECs 增加了 402.01%，同时伴随着凋亡蛋白的替代表达，即 Bax 的上调、Bcl-2 的下调、线粒体细胞色素 c 的释放和 caspase-9/caspase-3 的裂解。这些结果表明，CdTe QDs 不仅可以损害线粒体，还可以通过激活线粒体死亡途径和诱导内皮细胞凋亡来发挥内皮毒性。我们的结果提供了 QDs 对人血管内皮细胞直接毒性作用的有力证据，并表明暴露于 QDs 是心血管疾病发展的重大风险。这些结果还为 QDs 的未来安全使用和操作提供了有价值的指导，使其成为更适合纳米医学的工具。
