RARE EARTH NANOPROBES FOR OPTICAL IMAGING AND DISEASE TRACKING

项目描述（申请人提供）：用于光学成像和疾病跟踪的稀土纳米探针项目负责人：Prabhas V. Moghe，博士；Richard E. Riman博士；查尔斯M.罗斯博士合作者：Mark Pierce博士Shridar Ganesan医学博士该项目旨在开发一个新的纳米级成像探针库，以识别和动态跟踪引发转移性癌症和动脉粥样硬化等难以治疗的疾病快速扩散的微病变。这些疾病造成死亡率和发病率以及增加保健费用，目前给社会造成了惊人的损失。治疗这些疾病的技术正在显示出进步，但如果与早期诊断和药物治疗效果的快速反馈相结合，显然会产生更好的结果。在本R01提案中，我们试图通过推进可调谐的SWIR发射稀土纳米探针来利用光谱中迄今尚未开发的短波红外（SWIR）成像领域的变革潜力。我们的团队已经证明了一种新的稀土纳米探针家族的潜力，它比其他形式的光学荧光成像更深入地成像组织，并且具有很少的自身荧光和减少的散射。该项目的具体目标是开发新的SWIR成像探针和技术，以检测和跟踪体内微病变并确定其分子表型。本文将合成一种新型的具有高发光强度的多光谱稀土掺杂荧光粉纳米探针，并对其光子特性进行测试。这些探针有效标记和分辨来自工程的亚表面病变细胞簇的swr发射的能力将在体外进行基准测试（目的1）。Aim 2将优化三种用于SWIR探针的会聚体内成像工具，包括用于靶向乳腺癌细胞转移灶的生物功能化探针的设计，淋巴结病变的SWIR宏观成像以及病变的SWIR原位共聚焦显微镜。在Aim 3中，我们将研究病变靶向探针检测和跟踪药物治疗后体内转移性病变的发展和消退的能力。这项研究的结果将包括更灵敏地识别和阐明体内疾病病变的分子决定因素的新工具。潜在的应用包括淋巴结追踪的组织保留成像，用于癌症转移的早期检测，以及心血管疾病和动脉粥样硬化血栓形成等血管病变的成像。R01的预期影响将是一个一流的成像探针/硬件框架，相当于“体内光学活检”，以可视化疾病微病变的发生率，生长和治疗，超越目前可能的空间分辨率（“分子表型”）和检测亚表面病变组织（“深度渗透”）的限制。

DESCRIPTION (provided by applicant): Rare Earth Nanoprobes for Optical Imaging and Disease Tracking PIs: Prabhas V. Moghe, PhD,; Richard E. Riman,PhD; Charles M. Roth, PhD. Collaborators: Mark Pierce, PhD., Shridar Ganesan, MD, PhD. This project aims to develop a library of new nanoscale imaging probes to identify and dynamically track microlesions that trigger the rapid spread of difficult to treat diseases like metastatic cancers and atherothrombosis. By causing mortality and morbidity as well as increasing health care costs, these diseases currently take a staggering toll on society. Technologies to treat these diseases are showing improvements, but clearly would have better outcomes when integrated with early diagnoses and rapid feedback on the effectiveness of pharmacotherapy. In this R01 proposal, we seek to harness the transformative potential of a hitherto undeveloped region of the optical spectrum, short wave infrared (SWIR)-based imaging, by advancing tunable SWIR emitting rare earth nanoprobes. Our team has demonstrated the potential of a new family of rare earth nanoprobes to image deeper within tissues than other modalities of optical fluorescence imaging, and with little autofluorescence and reduced scattering. The specific goals of this project are to develop new SWIR imaging probes and technology to detect and track microlesions in vivo and to identify their molecular phenotype. A novel panel of multispectral rare earth doped phosphor nanoprobes with high luminescence intensity will be synthesized and tested for their photonic properties. The ability of these probes to effectively label and resolve the SWIR-emission from engineered, sub-surface diseased cell clusters will be benchmarked in vitro (Aim 1). A suite of three convergent in vivo imaging tools for the SWIR probes will be optimized in Aim 2, including the design of biofunctionalized probes for targeting to metastatic lesions of breast cancer cells, SWIR macroscopic imaging of the lesions in the lymph nodes, and SWIR in situ confocal microscopy of lesions. In Aim 3, we will investigate the ability of the lesion-targeted probes to detect and track the development and regression of metastatic lesions in vivo following pharmacotherapy. Outcomes from this study will include new tools for more sensitively identifying and elucidating the molecular determinants of disease lesions in vivo. Potential applications include tissue- sparing imaging of lymph node tracking for early detection of cancer metastasis, as well as imaging of vascular lesions such as those in cardiovascular disease and atherothrombosis. The envisioned impacts of the R01 would be a first-in-class imaging probe/hardware framework, equivalent to an "optical biopsy in vivo", to visualize the incidence, growth, and treatment of disease microlesions, stretching beyond the currently possible limits of spatial resolution ("molecular phenotyping") and detection of sub-surface diseased tissues ("depth penetration").