Endoscopic molecular imaging of esophageal cancer with multiplexed Raman nanopart

使用多重拉曼纳米部件对食管癌进行内窥镜分子成像

• 批准号: 8283324
• 负责人: Jonathan T.C. Liu
• 金额: $ 26.11万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8283324
• 关键词: Agreement; Animals; Area; Back; Binding; Biological Markers; Cancer Model; Cell Line; Cell surface; Cessation of life; Collection; Devices; Diagnosis; Diagnostic Imaging; Diet; Disease; Disease Progression; Early Diagnosis; Endoscopes; Epidermal Growth Factor Receptor; Esophageal Squamous Cell Carcinoma; Esophagus; Etiology; Feasibility Studies; Fiber; Future; Genetic; Goals; Histopathology; Human; Image; Imagery; Imaging Device; Label; Lasers; Lighting; Malignant Neoplasms; Malignant neoplasm of esophagus; Modality; Modeling; Molecular; Molecular Target; Monitor; Neoplasm Metastasis; Patients; Pattern; Proteins; Protocols documentation; Rattus; Reproducibility; Resected; Sampling; Scanning; Secure; Sensitivity and Specificity; Signal Transduction; Solutions; Source; Squamous Cell; Staging; Surface; Techniques; Technology; Time; Tissues; Topical application; Toxic effect; Translations; Treatment Protocols; Work; base; design and construction; disease diagnosis; flexibility; improved; in vivo; molecular imaging; mortality; nanoparticle; nanosized; particle; protein expression; public health relevance; ratiometric; response; tumor progression; two-dimensional

DESCRIPTION (provided by applicant): Esophageal squamous cell carcinoma (ESCC) is responsible for approximately one-sixth of all cancer-related deaths worldwide. This malignancy is due to several environmental, dietary and genetic factors. Since esophageal cancer has often metastasized at the time of diagnosis, current treatment modalities offer poor survival and cure rates. There is a need for improved imaging diagnostics to screen for subtle changes that precede the onset of ESCC. Since ESCC originates from the squamous cells that line the inner surface of the esophagus, the imaging of altered protein expression (molecular biomarkers) at these surfaces could be used to monitor disease progression. However, due to the variability in molecular expression patterns between patients, and within a single patient over time, accurate disease diagnosis would benefit from the ability to image a large number of molecular targets. Therefore, we are developing an in vivo imaging device to image surface-enhanced Raman scattering (SERS) nanoparticles that are capable of being highly multiplexed to target a large number of protein biomarkers. This feasibility study will develop and demonstrate these technologies in a well-established rat model of ESCC. This two-year exploratory study will develop technologies, and provide evidence of feasibility, to enable future studies to visualize alterations in molecular expression that occur during the progression of ESCC in a rat model, as well as to investigate the molecular changes that occur in response to therapy. In the future, we will work with collaborators to develop SERS particles to target a variety of biomarkers that are relevant for this cancer model, as well as in humans. Our ultimate goal is to better understand the molecular transformations associated with cancer progression in this rat model as well as in human esophageal cancers, thus enabling accurate early detection, assessment of therapy response, and personalized treatments. Efforts are being made, including toxicity studies, to secure FDA approval for the translation of these imaging devices and nanoparticles into humans.

描述（由申请人提供）：食管鳞状细胞癌（ESCC）约占全球所有癌症相关死亡的六分之一。这种恶性肿瘤是由于几个环境，饮食和遗传因素。由于食管癌通常在诊断时已经转移，目前的治疗方式提供了较差的生存率和治愈率。需要改进的成像诊断来筛查ESCC发病前的细微变化。由于ESCC起源于食管内表面的鳞状细胞，因此这些表面的蛋白质表达改变（分子生物标志物）的成像可用于监测疾病进展。然而，由于患者之间以及单个患者内的分子表达模式随时间的变化，准确的疾病诊断将受益于对大量分子靶标成像的能力。因此，我们正在开发一种体内成像设备，以成像表面增强拉曼散射（Sers）纳米粒子，能够高度多路复用，以针对大量的蛋白质生物标志物。这项可行性研究将在一个成熟的ESCC大鼠模型中开发和证明这些技术。这项为期两年的探索性研究将开发技术，并提供可行性证据，使未来的研究能够可视化在大鼠模型中ESCC进展期间发生的分子表达变化，以及研究治疗反应中发生的分子变化。在未来，我们将与合作者合作开发Sers颗粒，以靶向与这种癌症模型以及人类相关的各种生物标志物。我们的最终目标是更好地了解与该大鼠模型以及人类食管癌中癌症进展相关的分子转化，从而实现准确的早期检测，评估治疗反应和个性化治疗。目前正在努力，包括毒性研究，以确保FDA批准将这些成像设备和纳米颗粒转化为人类。