Nanotechnology for Minimally Invasive Cancer Detection and Resection

用于微创癌症检测和切除的纳米技术 项目摘要 有效的手术切除是癌症患者生存最重要的预测因素。虽然 手术对大约45%的癌症患者是治愈的，高达40%的患者因 恶性和良性增生或正常组织之间无法察觉的差异，导致不完全 切除癌组织。此外，接受手术的患者往往生活质量下降。 由于与手术相关的伤势。癌症独立之路奖的主要目标 纳米技术研究(K99/R00)建议将纳米技术的独特能力与 创新的光学仪器，通过最小限度地提高对恶性组织的检测和切除 侵入性手术。这一挑战将通过将专业知识和研究方法结合在一起来解决 纳米技术、仪器和外科肿瘤学。这个职业发展奖有四个具体的 目标：(1)开发可生物降解和无毒的可激活荧光纳米颗粒探针；(2)开发一种 小型化、柔性化的术中荧光检测装置；(3)集成化、小型化、柔性化 具有内窥镜的光学设备，用于肿瘤的微创检测；以及(4)评估光谱 内窥镜在大型动物(犬)手术中使用自发性胸部肿瘤来改善疾病 清除和病理分期。实现这些具体目标将利用针对性和可激励性 纳米颗粒，以提高探针在癌症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的肿瘤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症并减少与手术相关的 发病率，如减少患者的疼痛、不适和残疾。我近期的职业目标是获得一份 终身教职，专注于将纳米技术与外科肿瘤学相结合。从长远来看，我 希望领导一个科学、医学和工程相结合的研究计划，并扩大 将调查的疾病的数量和类型。理想情况下，这项研究应该在 在这里，我可以与来自不同领域的学术和医学研究人员打交道。培训期间 这个奖项的指导阶段将集中在几个关键方面，以促进我的发展，以实现 作为一名独立调查员，这些目标包括(1)为候选人提供坚实的基础 光学纳米颗粒工程，(2)基于光纤的光谱和近红外成像仪器， (3)外科肿瘤学中微创腹腔镜手术的方法学挑战。 在导师的指导下，培训将在埃默里-佐治亚理工学院生物医学工程系进行 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，在宾夕法尼亚大学的共同指导下 苏尼尔·辛哈尔医生，医学博士，胸外科研究实验室主任兼胸科主任 手术。这两个机构的环境非常适合这个项目，因为我将完全访问 最先进的纳米颗粒设计、合成和表征仪器；我将受益于 拥有满足我需求的制造设施的仪器工程师；以及高度协作的翻译 环境，这对这个集成了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，合作培训将是 此外，埃默里和佐治亚理工学院还提供了光学和仪器方面的正式课程。

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.