Nanotechnology for Minimally Invasive Cancer Detection and Resection

用于微创癌症检测和切除的纳米技术

• 批准号: 8413972
• 负责人: Aaron M. Mohs
• 金额: $ 24.89万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8413972
• 关键词: Address; Animal Model; Animals; Artificial nanoparticles; Award; Benign; Biomedical Engineering; Caliber; Cancer Center; Cancer Detection; Cancer Patient; Cancerous; Canis familiaris; Clinical; Computers and Advanced Instrumentation; Contrast Media; Detection; Development; Devices; Diagnostic; Disease; Doctor of Medicine; Doctor of Philosophy; Drug Kinetics; Endoscopes; Endoscopy; Engineering; Environment; Excision; FDA approved; Faculty; Feedback; Fiber Optics; Fluorescence; Fluorescent Dyes; Foundations; Goals; Hemorrhage; Image; Indocyanine Green; Injury; Institution; International; K-Series Research Career Programs; Laboratory Research; Laparoscopic Surgical Procedures; Lead; Malignant - descriptor; Malignant Neoplasms; Medical; Medicine; Mentors; Mentorship; Methods; Modeling; Morbidity - disease rate; Nanotechnology; Nodule; Non-Small-Cell Lung Carcinoma; Normal tissue morphology; Operating Rooms; Operative Surgical Procedures; Optics; Pain; Pathological Staging; Pathology; Pathway interactions; Patients; Penetration; Pennsylvania; Phase; Polymers; Positioning Attribute; Primary Neoplasm; Procedures; Quality of life; Recovery; Recurrence; Recurrent tumor; Repeat Surgery; Research; Research Methodology; Research Personnel; Resected; Residual Cancers; Residual Tumors; Science; Sensitivity and Specificity; Spectrum Analysis; Surgeon; Surgical Oncology; Surgical incisions; Surgical margins; System; Techniques; Thoracic Neoplasms; Thoracic Surgical Procedures; Time; Tissues; Training; Tumor Tissue; Universities; Validation; abstracting; animal tissue; base; biocompatible polymer; biodegradable polymer; cancer surgery; career; clinical efficacy; clinically relevant; design; disability; flexibility; fluorophore; high risk; improved; innovation; instrumentation; intraoperative imaging; meetings; miniaturize; minimally invasive; mortality; nano; nanoparticle; nanoprobe; neoplastic cell; optical fiber; physical property; programs; self assembly; tumor

NANOTECHNOLOGY FOR MINIMALLY INVASIVE CANCER DETECTION AND RESECTION Project Abstract Effective surgical resection of tumors is the most important predictor for cancer patient survival. Although surgery is curative in approximately 45% of cancer patients, up to 40% of patients have recurrent tumors due to undetectable differences between malignant and benign hyperplasic or normal tissue, leading to incomplete resection of cancerous tissue. In addition, patients that undergo surgery often suffer a decreased quality of life due to injury associated with the surgery. The primary goal of this Pathway to Independence Award in Cancer Nanotechnology Research (K99/R00) proposal is to integrate the unique capabilities of nanotechnology with innovative optical instrumentation to improve detection and resection of malignant tissue through minimally invasive surgery. This challenge will be addressed by combining expertise and research methodology in nanotechnology, instrumentation, and surgical oncology. This career development award has four specific aims: (1) develop biodegradable and nontoxic activatable fluorescence nanoparticle probes; (2) develop a miniaturized and flexible device for intraoperative fluorescence detection; (3) integrate the miniaturized, flexible optical device with endoscopy for minimally invasive detection of tumors; and (4) evaluate the spectral endoscope using spontaneous thoracic tumors in large animals (canines) during surgery to improve disease clearance and pathological staging. Accomplishing these specific aims will utilize targeted and activatable nanoparticles to increase specific localization of the probes in cancerous tissue. Detecting and resecting cancerous tissue via the fiber optic endoscopic imaging system will decrease the rate of tumor recurrence by more accurately detecting surgical margins and residual cancer and reduce surgery associated morbidity, such as decreasing patient pain, discomfort, and disability. My immediate career goal is to obtain a tenure-track faculty position that focuses on integrating nanotechnology with surgical oncology. Long-term, I would like to lead a research program at the interface of science, medicine, and engineering and expand the number and types of diseases that will be investigated. Ideally this research would be performed at an institution where I can be involved with academic and medical investigators from diverse fields. Training during the mentored phase of this award will focus on several key aspects to facilitate my development to achieve these goals as an independent investigator, including (1) providing the candidate with a strong foundation in optical nanoparticle engineering, (2) instrumentation for fiber optic based spectral and near-infrared imaging, and (3) methodological challenges to minimally invasive laparoscopic procedures in surgical oncology. Training will take place in the Emory-Georgia Tech Biomedical Engineering Department under the mentorship of Dr. Shuming Nie, Ph.D., an international expert in nanotechnology and director of the Emory-Georgia Tech Center for Cancer Nanotechnology Excellence, and at the University of Pennsylvania under the co-mentorship of Dr. Sunil Singhal, M.D., Director of the Thoracic Surgery Research Laboratory and Chief of Thoracic Surgery. The environment at these two institutions is ideal for this project because I will have full access to the most advanced instrumentation for nanoparticle design, synthesis, and characterization; I will benefit from instrumentation engineers with fabrication facilities to meet my needs; and a highly collaborative translational environment, which is paramount for successful development of this project that integrates nanotechnology with minimally invasive intraoperative instrumentation. In addition, the collaborative training will be supplemented by formal coursework at Emory and Georgia Tech in optics and instrumentation.

用于微创癌症检测和切除的纳米技术 项目摘要 有效的肿瘤手术切除是癌症患者生存的最重要的预测因素。虽然 约 45% 的癌症患者接受手术治疗，高达 40% 的患者因肿瘤复发 恶性和良性增生或正常组织之间无法检测到的差异，导致不完全 切除癌组织。此外，接受手术的患者的生活质量通常会下降 由于手术相关的损伤。癌症独立之路奖的主要目标 纳米技术研究（K99/R00）提案是将纳米技术的独特能力与 创新的光学仪器，通过最小限度地改进恶性组织的检测和切除 侵入性手术。这一挑战将通过结合专业知识和研究方法来解决 纳米技术、仪器仪表和肿瘤外科。该职业发展奖有四个具体内容 目标：（1）开发可生物降解且无毒的可激活荧光纳米颗粒探针； (2) 开发一个 用于术中荧光检测的小型灵活装置； (3)集成化小型化、柔性化 用于肿瘤微创检测的内窥镜光学装置； (4) 评估光谱 内窥镜在手术期间使用大型动物（犬科动物）的自发性胸部肿瘤来改善疾病 清除率和病理分期。实现这些具体目标将利用有针对性的和可激活的 纳米颗粒以增加探针在癌组织中的特异性定位。检测和切除 通过光纤内窥镜成像系统检测癌组织将降低肿瘤复发率 通过更准确地检测手术切缘和残留癌并减少手术相关 发病率，例如减少患者疼痛、不适和残疾。我的近期职业目标是获得 终身教授职位，专注于将纳米技术与肿瘤外科相结合。从长远来看，我 希望领导一个科学、医学和工程交叉领域的研究项目，并扩大 将调查的疾病的数量和类型。理想情况下，这项研究将在 我可以与来自不同领域的学术和医学研究人员一起参与的机构。训练期间 该奖项的指导阶段将重点关注几个关键方面，以促进我的发展以实现 作为独立调查员的这些目标，包括（1）为候选人提供坚实的基础 光学纳米粒子工程，（2）基于光纤的光谱和近红外成像仪器， (3) 肿瘤外科微创腹腔镜手术的方法学挑战。 培训将在埃默里-佐治亚理工学院生物医学工程系的指导下进行 国际纳米技术专家、埃默里-佐治亚理工学院院长聂树明博士 癌症纳米技术卓越中心，并在宾夕法尼亚大学共同指导下 Sunil Singhal 博士，医学博士，胸外科研究实验室主任兼胸外科主任 外科手术。这两个机构的环境对于这个项目来说是理想的，因为我将可以完全访问 最先进的纳米粒子设计、合成和表征仪器；我将受益于 拥有制造设施的仪器工程师可以满足我的需求；以及高度协作的翻译 环境对于这个集成纳米技术的项目的成功开发至关重要 使用微创术中器械。此外，合作培训还将 辅以埃默里大学和佐治亚理工学院光学和仪器方面的正式课程。