Computational and ultrastructural toxicology of a nanoparticle, Quantum Dot 705, in mice
Computational and ultrastructural toxicology of a nanoparticle, Quantum Dot 705, in mice
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DOI：
10.1021/es800254a
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发表时间：
2008-08-15
影响因子：
11.4
通讯作者：
Yang, Raymond S. H.
中科院分区：
文献类型：
--
作者：
Lin, Pinpin;Chen, Jein-Wen;Yang, Raymond S. H.
我们在雄性ICR小鼠中单次静脉注射量子点705（QD 705）后进行了长达6个月的药代动力学和毒理学研究。在1、4和24小时; 3、7、14和28天;以及6个月时，对每组6只小鼠/时间点进行时程处死。还在24 h、28天和6个月时进行了质量平衡研究。使用电感耦合等离子体质谱法，分析各种组织，尿液和粪便中的镉（Cd 111），这是QD 705的主要（46%）成分。在这些实验研究的基础上，开发了一个基于生理的药代动力学计算机模拟模型，具有良好的预测能力的时间依赖性的动力学和组织中的分布变化的QD 705。QD 705在脾脏、肝脏和肾脏中持续存在和蓄积至少28天，几乎没有或没有处置，但在6个月时逐渐和部分消除。尽管通过光学显微镜检查发现脾脏、肝脏和肾脏的组织学变化不显著，但在给药后28天和6个月，使用电子显微镜对许多肾脏样本进行的研究显示肾小管上皮细胞中存在明确的线粒体变化。QD 705的健康影响和潜在的有益应用的建议。
We conducted pharmacokinetic and toxicology studies on Quantum Dot 705 (QD705) in male ICR mice for up to 6 months after a single intravenous dose. Time-course sacrifices were carried out at 1, 4, and 24 h; 3, 7, 14, and 28 days; and 6 months on groups of six mice per time point. Mass balance studies were also carried out at 24 h, 28 days, and 6 months. Using inductively coupled plasma mass spectrometry, various tissues, urine, and feces were analyzed for cadmium (Cd111), which is a major (46%) component of QD705. On the basis of these experimental studies, a physiologically based pharmacokinetic computer simulation model was developed with excellent predictive capability for the time-dependent kinetic and distributional changes of QD705 in tissues. QD705 persisted and accumulated in the spleen, liver, and kidneys for at least 28 days with little or no disposition but was gradually and partially eliminated by 6 months. Although histological alterations of the spleen, liver, and kidney by light microscopy are unremarkable investigation using electron microscopy on numerous renal samples revealed definitive mitochondrial alterations in renal tubular epithelial cells at 28 days and 6 months post dosing. Health implications and potential beneficial applications of QD705 are suggested.