In vivo biodistribution and toxicology studies of cadmium-free indium-based quantum dot nanoparticles in a rat model.
In vivo biodistribution and toxicology studies of cadmium-free indium-based quantum dot nanoparticles in a rat model.
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DOI：
10.1016/j.nano.2018.07.009
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发表时间：
2018-11
期刊：
影响因子：
--
通讯作者：
MacRobert AJ
中科院分区：
文献类型：
--
作者：
Yaghini E;Turner H;Pilling A;Naasani I;MacRobert AJ
量子点（QD）纳米粒子由于其优异的物理化学性质，在生物医学应用中是非常有前途的造影剂和探针。然而，对常用的镉基量子点的毒性担忧阻碍了它们向临床应用的转化。在这项研究中，我们描述了在体内的生物分布和毒理学铟为基础的水溶性量子点在大鼠静脉给药。在长达90天的生物分布测量表明，QD主要积累在肝脏和脾脏，具有类似的消除动力学皮下给药。通过比较光致发光测量与元素分析，发现了QD在肝脏中降解的证据。QD处理的大鼠在以12.5 mg/kg或50 mg/kg静脉内给药后24 h、1周和4周未观察到器官损伤或组织病理学病变。血清生化和全血细胞计数分析未发现毒性。这项工作支持了铟基量子点转化为临床的强大潜力。量子点（QD）纳米粒子作为一类新的荧光探针在生物医学领域的应用正在兴起。然而，基于镉的QD的毒性问题阻碍了它们向临床环境的转化。在这项研究中，我们系统地研究了无镉铟基量子点在大鼠模型中的体内生物分布和毒理学。静脉注射后，大部分QD在肝脏和脾脏中积累，并在90天内从体内排出，元素分析证明了这一点。使用组织学评估、血液学和生物化学标记物的全面体内毒理学研究证明了铟基QD用于生物医学应用的生物相容性。
Quantum dot (QD) nanoparticles are highly promising contrast agents and probes for biomedical applications owing to their excellent photophysical properties. However, toxicity concerns about commonly used cadmium-based QDs hinder their translation to clinical applications. In this study we describe the in vivo biodistribution and toxicology of indium-based water soluble QDs in rats following intravenous administration. The biodistribution measured at up to 90 days showed that QDs mainly accumulated in the liver and spleen, with similar elimination kinetics to subcutaneous administration. Evidence for QD degradation in the liver was found by comparing photoluminescence measurements versus elemental analysis. No organ damage or histopathological lesions were observed for the QDs treated rats after 24 h, 1 and 4 weeks following intravenous administration at 12.5 mg/kg or 50 mg/kg. Analysis of serum biochemistry and complete blood counts found no toxicity. This work supports the strong potential of indium-based QDs for translation into the clinic. Quantum dot (QD) nanoparticles are emerging as a new class of fluorescence probes for biomedical applications. However, toxicity concerns of cadmium-based QDs hinder their translation to clinical settings. In this study we systemically investigated the in vivo biodistribution and toxicology of cadmium-free indium-based QDs in a rat model. Following intravenous injection the majority of QDs were accumulated in the liver and spleen and were excreted from the body over a period of ninety days as evidenced by elemental analysis. Comprehensive in vivo toxicology studies using histological assessments, hematological and biochemical markers demonstrated the biocompatibility of indium-based QDs for biomedical applications.
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