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: 7944053
• 负责人: SHUMING NIE
• 金额: $ 101.76万
• 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 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7944053
• 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）：此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，以在癌症手术中进行广泛应用。该手术纳米技术的重点的基本原理是，手术目前治愈所有癌症患者的45％，而化学疗法和放射治疗只能治愈5％。实际上，几乎所有癌症的患者存活率最重要的预测因子是通过去除原发性肿瘤，排出淋巴结和小的相邻卫星结节的完整手术切除。对于人肺，乳房，前列腺，结肠和胰腺癌，与部分或不完全切除相比，完整切除术的生存率有3至5倍。在过去的50年中，在改善术中技术方面几乎没有取得进展，目前，接受手术的40％以上的患者仍离开手术室，但由于遗漏的病变而没有完全切除。因此，存在开发纳米颗粒剂和术中仪器的主要机会，这些仪器将使外科医生在癌症手术过程中可视化显微镜肿瘤，转移性淋巴结和邻近的正常组织。这有可能对正在接受癌症手术的大量患者产生巨大影响。为了实现这一目标，我们在这里提出了一项翻译和协作计划，其中涉及三个学术机构（Emory，Georgia Tech和宾夕法尼亚大学）的7位高级教师研究人员，并在纳米技术，生物计算，分子成像，肿瘤手术和医学肿瘤学上进行了广泛的专业知识。整个项目是为了加速发展和临床影响的加速发展和临床影响，该项目将重点介绍三个主要努力：（1）基于质子化的胶体金和表面增强的拉曼散射（SERS）（Nie and and Coworkers）（Nie and Coworkers，Nature Biotech 26，83-90，2008-90，2008-90，2008）; （2）术中癌症检测和可视化的系统集成和实施，尤其是使用手持“点和检测”设备； （3）转化实验表明纳米技术在侵袭性肿瘤的动物模型（如肺癌，胰腺癌和转移性乳腺癌）中的手术应用。拟议的研究最终可能会影响降低这些和其他人类恶性肿瘤的当前高死亡率。一旦开发，纳米颗粒剂和微型光学设备也可以用于机器人和微创手术，例如内镜和腹腔镜手术，以检测和切除实体瘤。预计该项目将产生几种实际结果，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，用于癌症检测，软件和数据库，用于多重光谱成像和组织识别以及新的就业机会。 公共卫生相关性：该赠款申请旨在开发用于癌症手术应用的新技术和创新技术。主要目标是帮助外科医生描绘肿瘤边缘，鉴定残留的肿瘤细胞和微转移酶，并确定肿瘤是否已被完全切除。预计这项工作最终会影响降低目前肺，胰腺和转移性乳腺癌的死亡率高。

项目成果

Stimuli-responsive nanoparticles for targeting the tumor microenvironment.

• DOI: 10.1016/j.jconrel.2015.08.050
• 发表时间: 2015-12-10
• 期刊: Journal of controlled release : official journal of the Controlled Release Society
• 作者: Du J;Lane LA;Nie S
• 通讯作者: Nie S

Local recurrence following lung cancer surgery: incidence, risk factors, and outcomes.

• DOI: 10.1016/j.suronc.2013.04.002
• 发表时间: 2013-09
• 期刊: SURGICAL ONCOLOGY-OXFORD
• 影响因子: 2.3
• 作者: Fedor, David;Johnson, W. Rainey;Singhal, Sunil
• 通讯作者: Singhal, Sunil

The More Exotic Shapes of Semiconductor Nanocrystals: Emerging Applications in Bioimaging.

半导体纳米晶体的更奇特形状：生物成像中的新兴应用。

• DOI: 10.1016/j.coche.2014.01.013
• 发表时间: 2014
• 期刊: Current opinion in chemical engineering
• 影响因子: 6.6
• 作者: Lim,SungJun;Smith,Andrew;Nie,Shuming
• 通讯作者: Nie,Shuming

Compact and blinking-suppressed quantum dots for single-particle tracking in live cells.

• DOI: 10.1021/jp5064325
• 发表时间: 2014-12-11
• 期刊: The journal of physical chemistry. B
• 作者: Lane LA;Smith AM;Lian T;Nie S
• 通讯作者: Nie S

Small portable interchangeable imager of fluorescence for fluorescence guided surgery and research.

• DOI: 10.7785/tcrt.2012.500400
• 发表时间: 2015-04
• 期刊: Technology in cancer research & treatment
• 影响因子: 2.8
• 作者: Okusanya OT;Madajewski B;Segal E;Judy BF;Venegas OG;Judy RP;Quatromoni JG;Wang MD;Nie S;Singhal S
• 通讯作者: Singhal S