Modulation of Qdot nanoparticle toxicity by glutathione in GCL transgenic mice

谷胱甘肽对 GCL 转基因小鼠 Qdot 纳米颗粒毒性的调节

• 批准号: 7626716
• 负责人: Terrance J Kavanagh
• 金额: $ 47.15万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-18 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7626716
• 关键词: Achievement; Address; Affect; Animals; Apoptosis; Area; Behavior; Biological Availability; Biological Sciences; Breathing; Cell Line; Cell Survival; Cells; Chemicals; Clinical; Cultured Cells; Dermal; Detection; Encapsulated; Engineering; Environmental Exposure; Enzymes; Epithelial Cells; Evaluation; Exposure to; Feces; Fluorescence; Fluorescent Dyes; Fluorescent Probes; Gel; Gene Expression; Glutamate Carboxypeptidase II; Glutamate-Cysteine Ligase; Glutathione; Goals; Health; Heavy Metals; Hepatocyte; Histopathology; Human; Image; Implant; In Vitro; Ink; Intravenous; Kidney; Knockout Mice; Life; Ligands; Ligase Gene; Link; Measures; Metabolism; Metals; Mind; Mitochondria; Molecular Profiling; Mus; Nanotechnology; Necrosis; Nucleic Acids; Occupational; Optics; Oral; Organ; Oxidation-Reduction; Oxidative Stress; Peptide antibodies; Plasma; Policy Making; Polymers; Predisposition; Preparation; Property; Prostatic Neoplasms; Proteins; Quantum Dots; Research; Research Personnel; Risk Assessment; Role; Route; Scientist; Semiconductors; Solid; Surface; Surface Properties; Testing; Time; Tissues; Toxic effect; Transgenic Mice; Transgenic Organisms; Tubular formation; Urine; Vanadium; Vascular Endothelial Cell; Work; absorption; antibody conjugate; bioimaging; biological systems; biomaterial compatibility; cell type; chemical stability; design; fluorophore; functional group; human tissue; imaging modality; in vivo; information gathering; innovation; interest; macrophage; mouse model; nanocrystal; nanomaterials; nanoparticle; nanoscale; novel; optical imaging; photonics; practical application; programs; quantum; sensor; small molecule; surface coating; tumor; uptake

DESCRIPTION (provided by applicant) Recent advances in nanotechnology have produced a new class of fluorescent nanoparticles, semiconductor quantum dots (QDs). These nanometer-sized crystals have unique photochemical and photophysical properties that are not available from either isolated molecules or bulk solids, and consequently have enabled new opportunities in many areas including optoelectronics, anti-counterfeiting inks, and photovoltaics. More recently, the research interest in QDs has shifted toward the life sciences, where material scientists, chemists and biologists are working together to develop these quantum-confined nanocrystals as fluorescent probes for biomedical imaging. Compared with organic dyes and fluorescent proteins, semiconductor QDs offer several unique advantages, such as size- and composition-tunable emission from visible to infrared wavelengths, large absorption coefficients across a wide spectral range, and very high levels of brightness and photostability. High-quality QDs are generally made from group II-VI and -V elements in the chemical periodic table including Cd and Hg, which are toxic heavy metals. Our preliminary results indicate that polymer-protected QDs remain intact in live cells and animals for up to 2-4 months and are non-toxic. But their long term degradation, metabolism, and clearance are still unknown, which will ultimately determine the suitability of QDs for biomedical applications. Furthermore, because QDs intended for applications other than biomedicine will not necessarily be designed with biocompatibility in mind, concerns have been raised regarding potential occupational and environmental exposures to QDs. In this context, we propose to systematically investigate the toxicity of QDs of different chemical compositions. We will focus on QDs that have practical applications in photonics, optics, solar cells, sensors and biomedical imaging. We hypothesize that the colloidal stability and nanomaterial surface properties such as surface ligands and functional groups will affect in vitro and in vivo behavior and toxicity of QDs. In order to address this hypothesis, this application will focus on innovations of nanoparticle synthesis and surface engineering, in vitro toxicity to multiple murine and human cell types, and in vivo toxicity in genetically modified mice. Information gathered from these studies will be valuable in helping to predict the role of various constituent metals on the toxicity of QDs, as well as in the design of cores and coatings that will optimize the desirable properties of these materials while minimizing their adverse health impacts. Such information will be useful in risk assessments of these materials, and thus help to inform regulatory policy making.

描述（由申请人提供） 纳米技术的最新进展产生了一类新的荧光纳米颗粒，半导体量子点（QD）。这些纳米尺寸的晶体具有独特的光化学和光物理特性，这些特性是孤立分子或散装固体所无法获得的，因此在许多领域，包括光电子学，防伪油墨和光化学领域，都有新的机会。最近，量子点的研究兴趣已经转向生命科学，材料科学家，化学家和生物学家正在共同努力开发这些量子限制纳米晶体作为生物医学成像的荧光探针。与有机染料和荧光蛋白相比，半导体量子点提供了几个独特的优势，例如从可见光到红外波长的尺寸和成分可调的发射，在宽光谱范围内的大吸收系数，以及非常高的亮度和光稳定性。高质量的QD通常由化学周期表中的II-VI族和-V族元素制成，包括有毒重金属Cd和Hg。我们的初步结果表明，聚合物保护的量子点在活细胞和动物中保持完整长达2-4个月，并且无毒。但是它们的长期降解、代谢和清除仍然是未知的，这将最终决定量子点在生物医学应用中的适用性。此外，由于预期用于生物医学以外的应用的QD不一定在设计时考虑到生物相容性，因此已经提出了关于QD的潜在职业和环境暴露的担忧。在这种情况下，我们建议系统地研究不同化学成分的量子点的毒性。我们将专注于量子点，在光子学，光学，太阳能电池，传感器和生物医学成像的实际应用。我们推测胶体的稳定性和纳米材料的表面性质，如表面配体和官能团，将影响量子点的体外和体内的行为和毒性。为了解决这一假设，本申请将重点关注纳米颗粒合成和表面工程的创新，对多种小鼠和人类细胞类型的体外毒性，以及转基因小鼠的体内毒性。从这些研究中收集的信息将有助于预测各种组成金属对QD毒性的作用，以及在设计核心和涂层时，优化这些材料的理想性能，同时最大限度地减少其对健康的不利影响。这些信息将有助于对这些材料进行风险评估，从而有助于为制定监管政策提供信息。