Raman Molecular Imaging for Early Detection of Colon Cancer

描述（由申请人提供）：每年有超过50,000人因结肠癌而丧生，使其成为美国第三大致命癌症。该项目的目的是利用独特的拉曼成像显微内窥镜检测分子靶向纳米颗粒来改善早期结肠癌筛查。一种能够快速非接触成像的扫描拉曼内窥镜装置将被建立并用于对目标二氧化硅封装的金基纳米颗粒进行成像。这些粒子产生拉曼光散射信号，并将在混合物中局部施用于结肠，使比率成像能够从目标粒子中减去背景信号。拉曼内窥镜使用激光照射纳米颗粒并检测非弹性散射光。我们将制造环形扫描拉曼内窥镜，用白光对结肠解剖进行成像，并利用靶向拉曼活性粒子对结肠癌生物标志物进行成像。拉曼内窥镜已被设计用于临床使用，但将在自发性肿瘤（Pirc大鼠）和原发性人类异种移植物中进行评估。去鉴定的人类结肠癌组织将在常规结肠镜检查中获得，并通过手术植入动物体内。我们将使用qPCR、western blot分析和免疫组织化学技术来评估这些人类结肠癌组织中各种结肠癌生物标志物的过表达。选择肿瘤靶向配体，将用于功能化我们的拉曼纳米颗粒造影剂的表面。我们将首先在大鼠身上评估肿瘤靶向效率和拉曼内窥镜的性能，然后在大型动物（猪）身上进行评估。虽然这种新的诊断策略并不局限于结肠，但由于肿瘤靶向配体的可用性，内窥镜兼容性，毒性降低以及改进这种恶性肿瘤检测的实际需求，我们有动力在结直肠癌中验证我们的方法。这种方法的风险很低，因为拉曼内窥镜已经在人类中使用过，而且金纳米颗粒相对惰性，一些结构已经被FDA批准。利用拉曼光谱的超灵敏检测和多路复用能力来检测癌症，可以作为一种强大的诊断工具，有可能显著影响癌症患者的生存率

DESCRIPTION (provided by applicant): Over 50,000 lives are lost annually due to colon cancer, making it the third deadliest cancer in the United States. The aim of this project is to improve early-stage colon cancer screening using a unique Raman imaging microendoscope to detect molecularly targeted nanoparticles. A scanning Raman endoscope device capable of fast non-contact imaging will be built and used to image targeted silica-encapsulated, gold-based nanoparticles. The particles produce a Raman light scattering signal and will be administered topically to the colon in mixtures that enable ratiometric imaging to subtract out background signal from that targeted particles. The Raman endoscope, using laser light, illuminates the nanoparticles and detects the inelastically scattered light. We will fabricate the circumferential-scanning Raman endoscope to image the colon anatomy with white light as well as colon cancer biomarkers with targeted Raman-active particles. The Raman endoscope has been designed for clinical use but will be evaluated with spontaneous tumors (Pirc rats) and primary human xenografts. De-identified human colon cancer tissues will be procured during routine colonoscopy and surgically implanted into animals. Overexpression of various colon cancer biomarkers will be assessed on these human colon cancer tissues using qPCR, western blot analysis and immunohistochemistry. Selected tumor-targeting ligands, will be used to functionalize the surface of our Raman nanoparticle contrast agents. We will assess tumor targeting efficiency and the performance of our Raman endoscope first in rats and then in large animals (porcine). Although this novel diagnostic strategy is not limited to the colon, we are motivated to validate our approach with colorectal cancer due to the availability of tumor-targeting ligands, endoscope compatibility, reduced toxicity and a real need for improved detection of this malignancy. The approach is expected to be low risk because Raman endoscopes have previously been used in humans and because gold based nanoparticles are relatively inert with some constructs already approved by the FDA. Harnessing the ultrasensitive detection and multiplexing capabilities of Raman spectroscopy for the detection of cancer could serve as a powerful diagnostic tool with the potential to significantly impact the survival rate of cancer patients by earlier cancer detection.