Modulation of Qdot nanoparticle toxicity by glutathione in GCL transgenic mice

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粒子--半导体量子点(Qds)。这些纳米晶体具有孤立分子或块状固体所不具备的独特的光化学和光物理特性，因此在光电子、防伪油墨和光伏等许多领域都带来了新的机会。最近，对量子点的研究兴趣已经转移到生命科学上，在生命科学中，材料科学家、化学家和生物学家正在共同努力，开发这些量子受限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质相比，半导体量子点具有一些独特的优势，如从可见光到红外波长的尺寸和组成可调的发射，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。高质量的量子点通常由化学元素周期表中的II-VI和-V族元素制成，包括Cd和Hg，这是有毒的重金属。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体内最多保持2-4个月的完好无损，并且是无毒的。但它们的长期降解、代谢和清除尚不清楚，这最终将决定量子点在生物医学应用中的适用性。此外，由于用于生物医学以外的其他用途的量子点在设计时不一定考虑到生物兼容性，因此人们对潜在的职业和环境中的量子点暴露提出了关注。在此背景下，我们建议系统地研究不同化学组成的量子点的毒性。我们将重点关注在光子学、光学、太阳能电池、传感器和生物医学成像方面具有实际应用的量子点。我们假设，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，将影响量子点的体内外行为和毒性。为了解决这一假说，这一应用将集中在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，以及对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量子点毒性的作用，并有助于设计芯和涂层，以优化这些材料的理想性能，同时将其对健康的不利影响降至最低。这些信息将有助于对这些材料进行风险评估，从而有助于为监管政策的制定提供信息。

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.