Nanotechnology for Multiplexed and Intraoperative Cancer Detection

用于多重和术中癌症检测的纳米技术

• 批准号: 7854062
• 负责人: SHUMING NIE
• 金额: $ 98.1万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7854062
• 关键词: Address; Affinity; Animal Model; Applications Grants; Basic Science; Benign; Biocompatible; Biological Markers; Breast; Breast Cancer Model; Cancer Detection; Cancer Patient; Clinical; Clinical Engineering; Clinical Medicine; Clinical Trials; Collaborations; Color; Comparative Study; Computer software; Computers and Advanced Instrumentation; Databases; Detection; Development; Devices; Dyes; Employment Opportunities; Engineering; Environment; Epidermal Growth Factor Receptor; Excision; FDA approved; Faculty; Fluorescence; Foundations; Goals; Gold; Gold Colloid; Hand; Human; Image; Imagery; Indocyanine Green; Institution; Joints; Lasers; Lead; Left; Lesion; Ligands; Lung; Lung Neoplasms; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of pancreas; Measurement; Medical; Medical Oncology; Micrometastasis; Microscopic; Modeling; Monitor; Nanotechnology; Nature; Neoplasm Metastasis; Nodule; Normal tissue morphology; Operating Rooms; Operative Surgical Procedures; Optics; Outcome; Outcome Study; Pancreas; Paper; Patients; Peer Review Grants; Pennsylvania; Primary Neoplasm; Procedures; Prostate; Publishing; Quantum Dots; Radiation therapy; Recurrence; Reporting; Research; Research Personnel; Resected; Residual Tumors; Resolution; Rheumatoid Arthritis; Robotics; Science; Semiconductors; Sensitivity and Specificity; Signal Transduction; Solid Neoplasm; Standardization; Surface; Surgeon; Surgical Oncology; System; Systems Integration; Techniques; Time; Tissues; Translating; Universities; Urokinase Plasminogen Activator Receptor; Work; base; biocomputing; cancer cell; cancer recurrence; cancer surgery; chemotherapy; college; design; experience; folate-binding protein; improved; innovation; innovative technologies; instrument; instrumentation; lymph nodes; malignant breast neoplasm; medical schools; miniaturize; minimally invasive; molecular imaging; mortality; nanoparticle; nanoprobe; neoplastic cell; new technology; prevent; programs; prototype; public health relevance; research study; spectroscopic imaging; tumor; tumor xenograft

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.

描述（由申请人提供）：该 GO 拨款申请旨在整合纳米技术和创新光学仪器的独特功能，以在癌症手术中广泛应用。这种外科纳米技术重点的理由是，手术目前治愈了大约 45% 的癌症患者，而化疗和放射疗法总共只能治愈 5%。事实上，几乎所有癌症患者生存的最重要预测因素是完整的手术切除，即切除原发肿瘤、引流淋巴结和相邻的小卫星结节。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三到五倍。近50年来，术中技术的改进进展甚微，目前超过40%的接受手术的患者仍因漏诊病灶而未能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存在重大机会，使外科医生能够在癌症手术期间观察微观肿瘤、转移淋巴结和邻近正常组织。这有可能对大量接受癌症手术的患者产生巨大影响。为了实现这一目标，我们在此提出一项转化和合作计划，涉及来自三个学术机构（埃默里大学、佐治亚理工学院和宾夕法尼亚大学）的 7 名高级教员研究人员，他们拥有跨越纳米技术、生物计算、分子成像、肿瘤手术和肿瘤内科的广泛专业知识。整个项目旨在两年内加速开发和临床影响，将重点关注三项主要工作：（1）基于聚乙二醇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（Nie 和同事，Nature Biotech.26, 83-90, 2008）； (2) 术中癌症检测和可视化的系统集成和实施，特别是使用手持式“指向和检测”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）动物模型中的应用。拟议的研究最终可能会对降低这些和其他人类恶性肿瘤目前的高死亡率产生影响。一旦开发出来，纳米粒子制剂和微型光学装置还可以用于机器人和微创手术，例如用于检测和切除实体瘤的内窥镜和腹腔镜手术。该项目预计将产生一些实际成果，包括用于多重癌症检测的标准化金纳米粒子、用于癌症检测的新型光谱和成像仪器、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。 公共健康相关性：这项拨款申请旨在开发用于癌症手术的新技术和创新技术。主要目标是帮助外科医生勾画肿瘤边缘，识别残留的肿瘤细胞和微转移，并确定肿瘤是否已完全切除。这项工作预计最终将对降低目前肺癌、胰腺癌和转移性乳腺癌的高死亡率产生影响。