RARE EARTH NANOPROBES FOR OPTICAL IMAGING AND DISEASE TRACKING

用于光学成像和疾病追踪的稀土纳米探针

• 批准号: 8674563
• 负责人: PRABHAS V MOGHE
• 金额: $ 55.33万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-15 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8674563
• 关键词: 3-Dimensional; Address; American; Benchmarking; Biological; Biopsy; Blood Vessels; Breast Cancer Cell; Breast Melanoma; Cardiovascular Diseases; Cations; Cells; Ceramics; Communicable Diseases; Confocal Microscopy; Contrast Media; Detection; Development; Diagnosis; Diagnostic; Disease; Disseminated Malignant Neoplasm; Doctor of Philosophy; Drug Delivery Systems; Early Diagnosis; Effectiveness; Employee Strikes; Engineering; Exhibits; Family; Feedback; Figs - dietary; Fingerprint; Generations; Goals; Growth; Health Care Costs; Healthcare; Histologic; Histology; Image; Imaging Device; Imaging technology; In Situ; In Vitro; Incidence; Infrared Rays; Label; Lead; Lesion; Libraries; Lymphatic System; Lymphedema; Malignant Neoplasms; Medicine; Metastatic Lesion; Metastatic to; Methods; Minority; Modality; Molecular; Molecular Profiling; Monitor; Morbidity - disease rate; Neoplasm Metastasis; Neoplasms; Nerve Degeneration; Operative Surgical Procedures; Optical Biopsy; Optics; Outcome; Outcome Study; Patients; Penetration; Pharmacotherapy; Phenotype; Procedures; Property; Proteins; Research Personnel; Resected; Resolution; Risk; Sentinel Lymph Node; Short Waves; Societies; Specificity; Staging; Stretching; Surface; Technology; Testing; Therapeutic; Time; Tissues; Vision; Work; atherothrombosis; base; biological systems; biomaterial compatibility; body system; burden of illness; cardiovascular imaging; design; fluorescence imaging; imaging probe; in vivo; in vivo imaging; innovation; luminescence; lymph nodes; malignant breast neoplasm; millimeter; molecular phenotype; mortality; mouse model; multidisciplinary; nanomaterials; nanoparticle; nanoprobe; nanoscale; nanoshell; novel; operation; optical imaging; photonics; plaque lesion; public health relevance; response; tissue processing; tool

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").

描述（由申请人提供）：用于光学成像和疾病追踪的稀土纳米探针 PI：Prabhas V. Moghe，博士；理查德·E·里曼，博士；查尔斯·M·罗斯博士。合作者：Mark Pierce 博士、Shridar Ganesan 医学博士、博士。该项目旨在开发一个新的纳米级成像探针库，以识别和动态跟踪微病变，这些微病变会引发转移性癌症和动脉粥样硬化血栓等难以治疗的疾病的快速扩散。这些疾病导致死亡率和发病率以及医疗费用的增加，目前对社会造成了惊人的损失。治疗这些疾病的技术正在取得进展，但如果与早期诊断和药物治疗有效性的快速反馈相结合，显然会产生更好的结果。在这项 R01 提案中，我们寻求通过推进可调谐 SWIR 发射稀土纳米探针，来利用迄今为止尚未开发的光谱区域、基于短波红外 (SWIR) 的成像的变革潜力。我们的团队已经证明了一系列新的稀土纳米探针的潜力，可以比其他光学荧光成像方式在组织内更深入地成像，并且几乎没有自发荧光并减少了散射。该项目的具体目标是开发新的短波红外成像探针和技术来检测和跟踪体内微病变并识别其分子表型。将合成具有高发光强度的新型多光谱稀土掺杂磷光体纳米探针面板并测试其光子特性。这些探针有效标记和解析工程化的表面下患病细胞簇的短波红外发射的能力将在体外进行基准测试（目标 1）。目标 2 将优化一套用于 SWIR 探针的三种融合体内成像工具，包括设计用于靶向乳腺癌细胞转移性病变的生物功能化探针、淋巴结病变的 SWIR 宏观成像以及病变的原位共聚焦显微镜检查。在目标 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。这项研究的成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。潜在的应用包括用于早期检测癌症转移的淋巴结追踪的组织保留成像，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、生长和治疗，超出了目前可能的限制。空间分辨率（“分子表型”）和表面下病变组织的检测（“深度穿透”）。