期刊
BIOMATERIALS
卷 31, 期 32, 页码 8198-8209出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2010.07.069
关键词
Silica nanoparticles; Human umbilical vein endothelial cells (HUVECs); Oxidative stress; Apoptosis; Inflammation
资金
- Natural Science Foundation of China [30670556, 30470479]
- Shanghai Sci-Tech Committee Foundation [0752nm026]
- Shanghai Leading Academic Discipline Project [S30206]
Drug carriers are generally introduced into the body intravenously and directly exposed to endothelial cells. Silica nanoparticles could be promising delivery vehicles for drug targeting or gene therapy. However, few studies have been undertaken to determine the biological behavior of silica nanoparticles on endothelial cells. Here we measured reactive oxygen species (ROS) generation, apoptosis and necrosis, proinflammatory and prothrombic properties and the levels of the apoptotic signaling proteins and the transcription factors in human umbilical vein endothelial cells (HUVECs) after exposure to silica nanoparticles of different concentrations (25, 50, 100, and 200 mu g/mL) for 24 h. The results showed that silica nanoparticles, ranging from 50 mu g/mL to 200 mu g/mL, markedly induced ROS production, mitochondrial depolarization and apoptosis in HUVECs. At the highest concentration, the necrotic rate, LDH leakage, the expression of CD54 and CD62E, and the release of TF, IL-6, IL-8 and MCP-1 were significantly increased. Silica nanoparticles also activated c-Jun N-terminal kinase (INK), c-Jun, p53, caspase-3 and NF-kappa B, increased Bax expression and suppressed Bcl-2 protein. Moreover, inhibition of ROS attenuated silica nanoparticles-induced apoptosis and inflammation and the activation of JNK, c-Jun, p53 and NF-kappa B. In summary, our findings demonstrated that silica nanoparticles could induce dysfunction of endothelial cells through oxidative stress via JNK, p53 and NF-kappa B pathways, suggesting that exposure to silica nanoparticles may be a significant risk for the development of cardiovascular diseases such as atherosclerosis and thrombus. (C) 2010 Elsevier Ltd. All rights reserved.
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