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

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 mu g/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 mu g/mL CdTe QDs elicited significant oxidative stress, mitochondrial network fragmentation as well as disruption of mitochondrial membrane potential (Delta psi(m)); whereas ROS scavenger could protect HUVECs from QDs-induced mitochondrial dysfunction. Moreover, upon 24h exposure to 10 mu g/mL CdTe QDs, the apoptotic HUVECs dramatically increased by 402.01%, accompanied with alternative expression of apoptosis proteins, which were upregulation of Bax, down-regulation 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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.