Nanotechnology for Minimally Invasive Cancer Detection and Resection

描述（由申请人提供）：肿瘤的有效手术切除是癌症患者生存的最重要预测因素。虽然手术在大约45%的癌症患者中是治愈性的，但是高达40%的患者由于恶性和良性增生或正常组织之间的不可检测的差异而具有复发性肿瘤，导致癌组织的不完全切除。此外，接受手术的患者通常由于与手术相关的损伤而遭受生活质量下降。癌症纳米技术研究独立奖（K99/R 00）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，通过微创手术改善恶性组织的检测和切除。这一挑战将通过结合纳米技术，仪器和外科肿瘤学的专业知识和研究方法来解决。该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活化荧光纳米粒子探针;（2）开发用于术中荧光检测的小型化和灵活的设备;（3）将小型化，灵活的光学设备与内窥镜结合，用于肿瘤的微创检测。以及（4）在手术期间使用大型动物（犬）中的自发性胸部肿瘤来评估光谱内窥镜，以改善疾病清除和病理分期。实现这些特定目标将利用靶向和可活化的纳米颗粒来增加探针在癌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癌组织将通过更准确地检测手术切缘和残留癌症来降低肿瘤复发率，并降低手术相关的发病率，例如降低患者疼痛、不适和残疾。我近期的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，我想在科学，医学和工程的接口领导一个研究计划，并扩大将被调查的疾病的数量和类型。理想情况下，这项研究将在一个我可以与来自不同领域的学术和医学研究人员参与的机构进行。在该奖项的指导阶段的培训将集中在几个关键方面，以促进我的发展，以实现这些目标，作为一个独立的研究者，包括（1）提供候选人在光学纳米粒子工程的坚实基础，（2）仪器光纤为基础的光谱和近红外成像，和（3）在外科肿瘤微创腹腔镜手术的方法挑战。培训将在埃默里-佐治亚理工学院生物医学工程系进行，由Shuming Nie博士指导，纳米技术的国际专家和埃默里-佐治亚理工学院癌症纳米技术卓越中心主任，并在宾夕法尼亚大学的Sunil Singhal博士的共同指导下，胸外科研究实验室主任和胸外科主任。这两个机构的环境非常适合这个项目，因为我将有充分的机会使用最先进的纳米粒子设计，合成和表征仪器;我将受益于仪器工程师的制造设施，以满足我的需求;和高度协作的翻译环境，这对于成功开发将纳米技术与微创手术器械相结合的项目至关重要。此外，在埃默里大学和格鲁吉亚理工学院的光学和仪器方面，合作培训将得到正式课程的补充。 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。这里进行的研究将开发使用纳米颗粒的方法，以帮助外科医生在使用微创内窥镜手术时区分肿瘤边缘和残留肿瘤。在微创腹腔镜手术下增加肿瘤轮廓的综合效果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.