Develop hybrid optical-magneto nanoprobes for tracking dendritic cells

描述（由申请人提供）：在过去的十年中，我们见证了非侵入性分子成像的发展和实施取得了巨大的进步，通过分子成像的早期检测和分期来表征癌症的表型。在这些技术中，光学和磁共振（MR）成像模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强大的信息，通过高灵敏度和深度穿透以及快速数据采集和处理的能力来检测小群体的细胞。因此，该领域目前的趋势是试图结合必要的成像模式，通过任何单一模式无法比拟的协同增强来提供优越的成像性能。在这个应用中，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由近红外（NIR）发射半导体量子点（QDs）连接到超顺磁性氧化铁（SPIO）纳米颗粒组成。此外，我们计划修改这种杂交探针，以产生一种膜渗透衍生物，用于跟踪dc在体内的迁移。在我们的初步实验中，我们合成了一个适合体内成像的量子点库，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%）。右旋糖酐交联负对比SPIO纳米颗粒也被开发出来。我们的假设是，如果开发成功，这种混合成像纳米探针可以使用光学和磁共振成像技术来跟踪小鼠模型中DCs的迁移模式。此外，我们希望通过HINP优化DCs迁移检测的灵敏度，改善这些免疫细胞的分布路线。公共卫生相关性：将开发由半导体量子点和超顺磁性氧化铁纳米颗粒制成的混合成像纳米探针，以累积增强光学和磁共振成像技术的能力。这种多模态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.