Develop hybrid optical-magneto nanoprobes for tracking dendritic cells

描述(申请人提供)：在过去的十年里，我们见证了非侵入性分子成像的开发和实施方面的巨大进步，以便通过使用分子成像进行早期检测和分期来确定癌症的表型特征。在这些技术中，光学和磁共振(MR)成像方式以惊人的速度发展。这种方法彻底改变了我们在基础研究和临床应用中检测疾病的方式。然而，尽管最近取得了成功，但从这些工作中获得的经验使我们相信，没有一种单一的成像模式可以有效地提供足够稳健的信息，通过高度敏感和深入的渗透并具有快速数据采集和处理的能力来检测少量细胞。因此，目前这一领域的趋势是试图结合所需的成像模式，通过任何单一模式无法比拟的协同增强来提供卓越的成像性能。在这一应用中，我们建议开发一种新型的混合成像纳米探针(HINP)，用于使用磁共振光学成像技术对树突状细胞(DC)进行高分辨率成像。HINP由连接在超顺磁性氧化铁(SPIO)纳米颗粒上的近红外(NIR)发射半导体量子点(QD)组成。此外，我们计划对这种混合探针进行改造，以产生一种膜透性的衍生物，用于跟踪DC在体内的迁移。在我们的初步实验中，我们合成了一个具有适合体内成像的特征的量子点库，包括水溶性、稳定性、精确可调的近红外发射和高量子产率(30%-70%)。还开发了葡聚糖交联负对比度SPIO纳米颗粒。我们的假设是，如果开发出这种混合成像纳米探针，可以使用光学和磁共振成像技术在小鼠模型中跟踪树突状细胞的迁移模式。此外，我们还希望通过HINP优化DC迁移检测的灵敏度，并改善这些免疫细胞的分布途径。与公共健康相关：将开发半导体量子点和超顺磁性氧化铁纳米颗粒的混合成像纳米探测器，以累积增强光学和磁共振成像技术的能力。这种多模式成像策略将扩展我们目前对癌症生物学的理解。

DESCRIPTION (provided by applicant): In the past decade, we have witnessed tremendous advances in the development and implementation of non- invasive molecular imaging in order to phenotypically characterize cancers through early detection, staging using molecular imaging. Among these techniques, optical and magnetic resonance (MR) imaging modalities have evolved with remarkable speed. This approach has revolutionized the way we detect the diseases in both basic research and clinical applications. Despite its recent success however, experiences obtained from these works has led us to believe that there is no single imaging modality which can effectively provide information that is sufficiently robust to detect small populations of cells through highly sensitive and deep penetration and with the capability of quick data acquisition and processing. Therefore, the current trend in this area attempts to combine the imaging modalities necessary to provide superior imaging properties through synergistic enhancements unmatched by any single modality. In this application, we propose to develop a novel hybrid imaging nanoprobe (HINP) for high resolution imaging of dendritic cells (DCs) using MR-optical imaging techniques. The HINP consists of near-infrared (NIR) emitting semiconductor quantum dots (QDs) tethered to superparamagnetic iron oxide (SPIO) nanoparticles. Further, we plan to modify this hybrid probe to generate a membrane-permeable derivative for tracking the migration of DCs in vivo. In our preliminary experiments, we synthesized a library of QDs with suitable characteristics for in vivo imaging, including water solubility, stability, precisely tunable NIR emissions and high quantum yields (30-70%). The dextran cross-linked negative contrast SPIO nanoparticles have also been developed. Our hypothesis is that, if developed, this hybrid imaging nanoprobe could be used to track the migration patterns of DCs in a mouse model using optical and MR imaging techniques. Additionally, we want to optimize the sensitivity of DCs migration detection via HINP and improve the distribution route of these immunological cells. PUBLIC HEALTH RELEVANCE: Hybrid imaging nanoprobes from semiconductor quantum dots and superparamagnetic iron oxide nanoparticles will be developed for cumulative enhancing both optical and magnetic resonance imaging techniques capabilities. This multimodal imaging strategy will extend our current understanding of cancer biology.