Nanotechnology for Multiplexed and Intraoperative Cancer Detection

描述（由申请人提供）：这项GO拨款申请旨在整合纳米技术和创新光学仪器的独特能力，以广泛应用于癌症手术。这种手术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，而化疗和放疗加起来只治愈了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的手术切除，通过切除原发肿瘤，引流淋巴结和邻近的小卫星结节。对于人类肺癌、乳腺癌、前列腺癌、结肠癌和胰腺癌，研究表明，与部分或不完全切除相比，完全切除的生存率提高了3至5倍。近50年来，术中技术的进步甚微，目前仍有超过40%的手术患者因遗漏病灶而未完全切除而离开手术室。因此，开发纳米颗粒制剂和术中器械将使外科医生能够在癌症手术中看到显微镜下的肿瘤、转移性淋巴结和邻近的正常组织，这是一个重大机遇。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转化和合作项目，涉及三个学术机构（埃默里大学、佐治亚理工学院和宾夕法尼亚大学）的7名高级教师研究人员，他们在纳米技术、生物计算、分子成像、肿瘤外科和医学肿瘤学方面拥有广泛的专业知识。为了在两年内加速开发和临床效果，整个项目将集中在三个主要方面：(1)基于聚醚化胶体金和表面增强拉曼散射（SERS）的新型生物相容性和无毒纳米颗粒探针的优化和标准化（聂和同事，自然生物技术，26,83 -90,2008）；(2)术中肿瘤检测和可视化的系统集成与实现，特别是使用手持“点与检测”设备；(3)转化实验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）动物模型中的外科应用。拟议的研究最终可能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。一旦开发成功，纳米粒子制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，以检测和切除实体肿瘤。该项目预计将产生几个实际成果，包括用于多路癌症检测的标准化金纳米颗粒，用于癌症检测的新型光谱和成像仪器，用于多路光谱成像和组织识别的软件和数据库，以及新的就业机会。

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.