Endoscopic molecular imaging of esophageal cancer with multiplexed Raman nanopart

描述(申请人提供)：食道鳞状细胞癌(ESCC)约占全球所有癌症相关死亡病例的六分之一。这种恶性疾病是由几个环境、饮食和遗传因素造成的。由于食道癌通常在确诊时已经转移，目前的治疗方法存活率和治愈率都很低。需要改进的影像诊断方法来筛查ESCC发病前的细微变化。由于ESCC起源于排列在食道内表面的鳞状细胞，对这些表面改变的蛋白表达(分子生物标记物)的成像可以用于监测疾病的进展。然而，由于随着时间的推移，患者之间以及单个患者内部的分子表达模式存在差异，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对表面增强拉曼散射(SERS)纳米颗粒进行成像，这些纳米颗粒能够高度复合来靶向大量的蛋白质生物标记物。这项可行性研究将在成熟的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在大鼠模型ESCC进展过程中发生的分子表达变化，以及调查治疗后发生的分子变化。在未来，我们将与合作者合作开发SERS颗粒，以瞄准与这种癌症模型相关的各种生物标记物，以及在人类中。我们的最终目标是更好地了解在这个大鼠模型中以及在人类食道癌中与癌症进展相关的分子变化，从而能够准确地早期发现、评估治疗反应和个性化治疗。目前正在进行包括毒性研究在内的努力，以确保FDA批准将这些成像设备和纳米颗粒转化为人体。

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.