Endoscopic molecular imaging of esophageal cancer with multiplexed Raman nanopart

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。这种恶性肿瘤是由几种环境、饮食和遗传因素引起的。由于食管癌经常在诊断时转移，目前的治疗方式提供较低的生存率和治愈率。有必要改进成像诊断，以筛查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，因此这些表面蛋白表达改变（分子生物标志物）的成像可用于监测疾病进展。然而，由于患者之间的分子表达模式的可变性，以及单个患者随着时间的推移，准确的疾病诊断将受益于对大量分子靶点进行成像的能力。因此，我们正在开发一种体内成像设备来成像表面增强拉曼散射（SERS）纳米颗粒，这种纳米颗粒能够高度复用以靶向大量蛋白质生物标志物。这项可行性研究将在一个成熟的ESCC大鼠模型中开发和演示这些技术。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ESCC大鼠模型进展过程中分子表达的变化，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这种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、治疗反应评估和个性化治疗。人们正在努力，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。

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.