Nanotechnology for Multiplexed and Intraoperative Cancer Detection

描述（由申请人提供）：该GO赠款申请旨在整合纳米技术和创新光学仪器的独特功能，以广泛应用于癌症手术。这种外科纳米技术的基本原理是，手术目前治愈了大约45%的癌症患者，而化疗和放疗加在一起只能治愈5%。事实上，几乎所有癌症患者生存的唯一最重要的预测因素是完全手术切除，通过切除原发肿瘤，引流淋巴结和相邻的小卫星结节。对于人肺癌、乳腺癌、前列腺癌、结肠癌和胰腺癌，已经表明，与部分或不完全切除相比，完全切除具有三至五倍的生存改善。在过去的50年里，在改善术中技术方面几乎没有取得进展，目前超过40%的接受手术的患者仍然由于遗漏病变而没有完全切除而离开手术室。因此，主要的机会存在于开发纳米颗粒剂和术中仪器，其将允许外科医生在癌症手术期间可视化微观肿瘤、转移性淋巴结和邻近的正常组织。这有可能对更多接受癌症手术的患者产生巨大影响。为了实现这一目标，我们在这里提出了一个翻译和合作计划，涉及7名高级教师在三个学术机构（埃默里大学，格鲁吉亚理工学院和宾夕法尼亚大学）的调查人员，具有广泛的专业知识，横跨纳米技术，生物计算，分子成像，肿瘤外科和医学肿瘤学。为了在两年内加速开发和临床影响，整个项目将集中在三个主要方面：（1）基于聚乙二醇化胶体金和表面增强拉曼散射（Sers）的一类新的生物相容性和无毒纳米粒子探针的优化和标准化（Nie和同事，Nature Biotech. 26，83-90，2008）;（2）用于术中癌症检测和可视化的系统集成和实现，特别是通过使用手持式“指向和检测”装置;和（3）证明纳米技术在侵袭性肿瘤（如肺癌、胰腺癌和转移性乳腺癌）的动物模型中的手术应用的转化实验。这项拟议中的研究最终可能会对降低目前这些和其他人类恶性肿瘤的高死亡率产生影响。一旦开发出来，纳米粒子试剂和微型光学装置也可用于机器人和微创手术，如内窥镜和腹腔镜手术，以检测和切除实体瘤。该项目预计将产生几个实际成果，包括用于多重癌症检测的标准化金纳米颗粒，用于癌症检测的新光谱和成像仪器，用于多重光谱成像和组织识别的软件和数据库，以及新的就业机会。 公共卫生相关性：该拨款申请旨在开发用于癌症手术的新技术和创新技术。主要目的是帮助外科医生描绘肿瘤边缘，识别残留的肿瘤细胞和微转移，并确定肿瘤是否已被完全切除。这项工作有望最终对降低目前肺癌、胰腺癌和转移性乳腺癌的高死亡率产生影响。

DESCRIPTION (Provided by the applicant): This GO grant application aims to integrate the unique capabilities of nanotechnology and innovative optical instrumentation for broad applications in cancer surgery. The rationale for this surgical nanotechnology focus is that surgery currently cures approximately 45% of all patients with cancer, while chemotherapy and radiation therapy together only cure 5%. In fact, the single most important predictor of patient survival for almost all cancers is a complete surgical resection, by removing the primary tumor, draining lymph nodes and small adjacent satellite nodules. For human lung, breast, prostate, colon and pancreatic cancers, it has been shown that complete resection has a three to five fold improvement in survival compared to partial or incomplete resection. In the last 50 years, little progress has been made in improving intraoperative techniques, and currently over 40% of patients that undergo surgery still leave the operating room without a complete resection due to missed lesions. Thus, major opportunities exist to develop nanoparticle agents and intraoperative instrumentation that would allow a surgeon to visualize microscopic tumors, metastatic lymph nodes, and adjacent normal tissues during cancer surgery. This has the potential to make an enormous impact on a larger number of patients undergoing cancer surgery. Toward this goal, we propose here a translational and collaborative program involving 7 senior faculty investigators at three academic institutions (Emory, Georgia Tech, and the University of Pennsylvania) with broad expertise cutting across nanotechnology, biocomputing, molecular imaging, oncologic surgery, and medical oncology. Designed for accelerated development and clinical impact within two years, the overall project will focus on three major efforts: (1) optimization and standardization of a new class of biocompatible and nontoxic nanoparticle probes based on pegylated colloidal gold and surface-enhanced Raman scattering (SERS) (Nie and coworkers, Nature Biotech. 26, 83-90, 2008); (2) systems integration and implementation for intraoperative cancer detection and visualization, especially by using handheld "point-and-detect" devices; and (3) translational experiments demonstrating nanotechnology surgical applications in animal models of aggressive tumors such as lung cancer, pancreatic cancer, and metastatic breast cancer. The proposed research could ultimately make an impact in reducing the currently high mortality rates of these and other human malignancies. Once developed, the nanoparticle agents and miniaturized optical devices can also be used for robotic and minimally invasive surgery, such as endoscopic and laparoscopic procedures to detect and resect solid tumors. This project is expected to yield several practical outcomes including standardized gold nanoparticles for multiplexed cancer detection, new spectroscopic and imaging instruments for cancer detection, software and databases for multiplexed spectral imaging and tissue identification, as well as new employment opportunities. Public Health Relevance: This grant application aims to develop new and innovative technologies for applications in cancer surgery. The main goals are to help the surgeon to delineate tumor margins, to identify residual tumor cells and micrometastases, and to determine if the tumor has been completely removed. This work is expected to ultimately make an impact in reducing the currently high mortality rates of lung, pancreatic and metastatic breast cancers.