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）造成全球所有与癌症相关的死亡的六分之一。这种恶性肿瘤是由于几种环境，饮食和遗传因素引起的。由于食管癌在诊断时经常转移，因此当前的治疗方式可提供较差的生存率和治愈率。需要改进成像诊断，以筛选ESCC发作之前的细微变化。由于ESCC源自将食管内表面沿着鳞状细胞，因此可以使用这些表面上蛋白质表达（分子生物标志物）的成像来监测疾病进展。但是，由于患者之间和单个患者内部分子表达模式的变化，准确的疾病诊断将受益于成像大量分子靶标的能力。因此，我们正在开发一个体内成像装置，以形象表面增强的拉曼散射（SERS）纳米粒子，该纳米粒子能够高度多重以靶向大量的蛋白质生物标志物。这项可行性研究将在ESCC的大鼠模型中开发并证明这些技术。这项为期两年的探索性研究将开发技术，并提供可行性的证据，以使未来的研究能够可视化大鼠模型中ESCC过程中发生的分子表达的变化，并研究响应治疗后发生的分子变化。将来，我们将与合作者合作开发SERS颗粒，以针对与该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该大鼠模型以及人类食管癌中与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。正在做出努力，包括毒性研究，以确保FDA批准这些成像设备和纳米颗粒转化为人类。