An in vitro study of vascular endothelial toxicity of CdTe quantum dots

• Published in: Toxicology (Amsterdam) Vol. 282; no. 3; pp. 94 - 103
• Main Authors: Yan, Ming, Zhang, Yun, Xu, Kedi, Fu, Tao, Qin, Haiyan, Zheng, Xiaoxiang
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ireland Ltd 11-04-2011; Elsevier
• Subjects: adverse effects; Apoptosi; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Cadmium Compounds - toxicity; cardiovascular diseases; Cell Culture Techniques; Cell Line; Cell Survival - drug effects; cell viability; cytochrome c; Dose-Response Relationship, Drug; Drug Carriers - chemistry; drugs; Emergency; endothelial cells; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Endothelial Cells - ultrastructure; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Endothelium, Vascular - ultrastructure; Farmakologisk forskning; flow cytometry; fluorescent antibody technique; Fysiologi och farmakologi; Humans; in vitro studies; Medical sciences; MEDICIN; MEDICINE; membrane potential; Membrane Potential, Mitochondrial - drug effects; Microscopy, Electron, Transmission; mitochondria; Mitochondria, Muscle - drug effects; Mitochondria, Muscle - ultrastructure; Mitochondrial dysfunction; mitochondrial membrane; nanomedicine; oxidative stress; Pharmacological research; Physiology and pharmacology; Quantum Dots; Reactive oxygen species; Reactive Oxygen Species - metabolism; risk; s Mitochondrial dysfunction; Surface Properties; Tellurium - toxicity; Thiomalates - chemistry; toxicity; Toxicology; Toxikologi; Vascular endothelial cells; Vascular endothelial cells; Reactive oxygen species; Mitochondrial dysfunction; Quantum dots; Apoptosis; Oxidative stress; Endothelial cell; Quantum dot; Toxicity; In vitro; Endothelium; Mitochondria; Cell death; Dysfunction; Blood vessel; Circulatory system
• ISSN: 0300-483X; 1879-3185; 1879-3185
• DOI: 10.1016/j.tox.2011.01.015

Abstract 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 (0.1–100 μg/mL) dose-dependently decreased the cell viability of HUVECs, indicating CdTe QDs induced significant endothelial toxicity. The flow cytometric and immunofluorescence results revealed that 10 μg/mL CdTe QDs elicited significant oxidative stress, mitochondrial network fragmentation as well as disruption of mitochondrial membrane potential (Δ ψ m ); whereas ROS scavenger could protect HUVECs from QDs-induced mitochondrial dysfunction. Moreover, upon 24 h exposure to 10 μg/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.