Nanotechnology for Minimally Invasive Cancer Detection and Resection

描述(申请人提供)：有效的手术切除肿瘤是癌症患者生存最重要的预测因素。虽然手术可以治愈大约45%的癌症患者，但由于无法检测到恶性和良性增生或正常组织之间的差异，高达40%的患者有复发的肿瘤，导致癌症组织的不完全切除。此外，接受手术的患者通常会因为手术相关的伤害而生活质量下降。这项癌症纳米技术研究独立奖(K99/R00)提案的主要目标是将纳米技术的独特能力与创新的光学仪器相结合，通过微创手术改进对恶性组织的检测和切除。这一挑战将通过结合纳米技术、器械和外科肿瘤学的专业知识和研究方法来解决。这一职业发展奖有四个具体目标：(1)开发可生物降解和无毒的可激活荧光纳米颗粒探测器；(2)开发术中荧光检测的微型和灵活设备；(3)将微型、灵活的光学设备与内窥镜相结合，以进行微创肿瘤检测；以及(4)评估光谱内窥镜，使用大型动物(犬)的自发胸部肿瘤，以提高疾病清晰度和病理分期。实现这些特定目标将利用靶向和可激活的纳米颗粒来提高探针在癌症组织中的特异性定位。通过光纤内窥镜成像系统检测和切除肿瘤组织将通过更准确地检测手术切缘和残留癌来降低肿瘤复发率，并减少手术相关的发病率，如减少患者的疼痛、不适和残疾。我的直接职业目标是获得一个终身教职，专注于将纳米技术与外科肿瘤学相结合。从长远来看，我想领导一个科学、医学和工程相结合的研究计划，并扩大将被调查的疾病的数量和类型。理想情况下，这项研究将在一个机构进行，在那里我可以与来自不同领域的学术和医学研究人员打交道。在该奖项的指导阶段，培训将集中在几个关键方面，以促进我作为一名独立研究员的发展，包括(1)为候选人提供光学纳米颗粒工程方面的坚实基础，(2)基于光纤的光谱和近红外成像仪器，以及(3)外科肿瘤学中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进行，培训将在国际纳米技术专家、埃默里-佐治亚理工学院癌症纳米技术卓越中心主任聂树明博士的指导下进行，在宾夕法尼亚大学的培训将在苏尼尔·辛哈尔博士的共同指导下进行，辛哈尔博士是胸外科研究实验室主任兼胸外科主任。这两家机构的环境非常适合这个项目，因为我将完全能够接触到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，这对这个将纳米技术与微创术中器械相结合的项目的成功开发至关重要。此外，合作培训还将得到埃默里和佐治亚理工学院在光学和仪器方面的正式课程的补充。 公共卫生相关性：这个职业发展奖旨在将新的和创新的纳米技术方法整合到癌症手术中。在这里进行的研究将开发使用纳米颗粒来辅助外科医生在使用微创内窥镜手术的同时区分肿瘤边缘和残留肿瘤的方法。在微创腹腔镜手术下增加肿瘤轮廓的综合作用将对降低癌症的高死亡率和手术相关的发病率产生深远的影响。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: This career development award seeks to integrate new and innovative nanotechnology methods in cancer surgery. The research performed here will develop methods using nanoparticles to assist surgeons in distinguishing tumor margins and residual tumors while using minimally invasive endoscopic surgery. The combined effect of increasing tumor delineation under minimally invasive laparoscopic surgery will have a profound impact on reducing the high mortality rates from cancer and the morbidity associated with surgery.