INVESTIGATING TOXICOLOGY OF THIOL-CAPPED QUANTUM DOTS OF CADMIUM AND LEAD

研究镉和铅的硫醇封端量子点的毒理学

• 批准号: 8357072
• 负责人: Zikri Arslan
• 金额: $ 10.41万
• 依托单位: JACKSON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357072
• 关键词: Address; Affinity; Alcohols; Analytical Chemistry; Analytical Toxicology; Animals; Behavior; Binding; Biological; Biological Assay; Blood; Blood specimen; Brain; Cadmium; Computer Simulation; Data; Deposition; Diagnostic; Disease; Dose; Drug Kinetics; Environmental Health; Exhibits; Feces; Fluorescence; Fluorescence Microscopy; Fluorescence Spectroscopy; Fluorescent Dyes; Glutathione; Goals; Heart; Heavy Metals; Histopathology; ICP-AES; Ions; Kidney; Lead; Life; Light; Lipid Peroxidation; Liver; Lung; Mass Spectrum Analysis; Measures; Metals; Methods; Microscopy; Minority; Nanotechnology; Optics; Organ; Pattern; Plasma; Property; Proteins; Quantum Dots; Rattus; Research; Safety; Site; Source; Structure; Sulfhydryl Compounds; Symptoms; Techniques; Therapeutic Uses; Tissues; Toxic effect; Toxicology; Training; Ultraviolet Rays; Urine; Water; bioaccumulation; bioimaging; bone; cadmium selenide; cadmium sulfide; dosage; in vivo; lead selenide; lead sulfide; nanomaterials; nanoparticle; nanotoxicology; particle; programs; thioglycerol; ultrafine particle; ultraviolet irradiation

TOXICOLOGY OF THIOL-CAPPED QUANTUM DOTS OF CADMIUM AND LEAD Research is proposed to elucidate toxicology and pharmacokinetics of thiol-capped CdSe, CdS, PbSe and PbS quantum dots (QDs) in vivo. These QDs exhibit bright, photo-stable and size-tunable fluorescence. Further, their ultrafine particles (2-6 nm) show dimensional similarity with proteins. Thus, they are potential alternatives to traditional fluorescent dyes as optical probes in biomedical imaging and diagnostics, provided that the safety issues associated with heavy metals (Cd and Pb) are resolved. Capping with thiols is a potential avenue to render these hazardous QDs safe for biomedical applications, but the safety and pharmacokinetics of capped QDs are not known. To be viable, the QDs must be stable in vivo and eliminated completely from the body. Our hypothesis is that thiol-capped QDs will not be totally innocuous when used for therapeutic purposes as they readily bind to biological molecules and bioaccumulate in the body. The cap will be removed in vivo resulting in the exposure of the whole body to hazardous QDs and heavy metals. To elucidate the lexicological consequences of exposure, rats will be exposed to thiol-capped QDs (2-6 nm) intravenously (IV) with and without irradiating the QDs by UV light. The specific aims of the project are to: 1) determine the elimination rate of QDs from the body; 2) determine the cap stability by measuring content of metal ions and QDs in the urine and blood; 3) determine the accumulation limits in critical organs, including the heart, liver, lungs, kidney, brain and the bones; 4) determine the toxic effects and localization of QDs; 5) statistically evaluate cap stability, bioaccumulation profile and toxic effects associated with QD type, dose and UV light exposure; and 6) develop a computational model of structure/toxicity to predict the factors contributing most to toxicity. Various analytical chemistry and toxicology methods will be used in combination with UV-visible, plasma source emission/mass spectroscopy and fluorescence microscopy to characterize QDs in the organs. The results of this project will advance our understanding of the safety and toxicology of thiol-capped QDs of CdSe, CdS, PbSe and PbS. Successful completion of the project will contribute greatly to achieving the overall goal of RCMI at JSU to increase the pool of highly trained minority professionals in environmental health and nanotoxicology research through competitive programs.

巯基量子点的毒性研究 镉和铅 本文对巯基修饰的CdSe、CdS、PbSe的毒理学和药代动力学进行了研究 和PbS量子点（QDs）。这些量子点具有亮度高、光稳定性好、尺寸可调等特点 荧光。此外，它们的超细颗粒（2-6 nm）显示出与蛋白质的尺寸相似性。因此，在本发明中， 它们是传统荧光染料在生物医学成像中作为光学探针的潜在替代品 和诊断，前提是与重金属（Cd和Pb）相关的安全问题得到解决。 用硫醇封端是使这些危险的量子点安全用于生物医学的潜在途径 这些应用是可行的，但加帽QD的安全性和药物动力学尚不清楚。为了可行，量子点 必须在体内稳定并从体内完全消除。我们的假设是， 当用于治疗目的时，QD将不是完全无害的，因为它们容易与生物活性物质结合。 分子和生物积累在体内。将在体内移除帽，导致暴露 有害的量子点和重金属为了阐明的词汇学后果 暴露后，大鼠将静脉内（IV）暴露于硫醇封端的QD（2-6 nm）， 用紫外光照射量子点。该项目的具体目标是：1）确定淘汰率 2）通过测量来自身体的QD中的金属离子和QD的含量来确定帽稳定性; 尿液和血液; 3）确定关键器官中的累积极限，包括心脏，肝脏，肺， QDs的毒性作用和定位; 5）统计学分析 评价与QD类型、剂量和紫外线相关的瓶盖稳定性、生物累积特征和毒性效应 光暴露;以及6）开发结构/毒性的计算模型以预测因素 对毒性贡献最大。将使用各种分析化学和毒理学方法， 结合紫外可见、等离子体源发射/质谱和荧光显微镜 来表征器官中的量子点该项目的结果将促进我们对 巯基封端的CdSe、CdS、PbSe和PbS量子点的安全性和毒理学。成功完成 该项目将大大有助于实现RCMI在JSU的总体目标，以增加高度 通过竞争，培训环境卫生和纳米毒理学研究方面的少数民族专业人员。 程序.