NANOTECHNOLOGY FOR MINIMALLY INVASIVE CANCER DETECTION AND RESECTIONProject AbstractEffective surgical resection of tumors is the most important predictor for cancer patient survival. Althoughsurgery is curative in approximately 45% of cancer patients, up to 40% of patients have recurrent tumors dueto undetectable differences between malignant and benign hyperplasic or normal tissue, leading to incompleteresection of cancerous tissue. In addition, patients that undergo surgery often suffer a decreased quality of lifedue to injury associated with the surgery. The primary goal of this Pathway to Independence Award in CancerNanotechnology Research (K99/R00) proposal is to integrate the unique capabilities of nanotechnology withinnovative optical instrumentation to improve detection and resection of malignant tissue through minimallyinvasive surgery. This challenge will be addressed by combining expertise and research methodology innanotechnology, instrumentation, and surgical oncology. This career development award has four specificaims: (1) develop biodegradable and nontoxic activatable fluorescence nanoparticle probes; (2) develop aminiaturized and flexible device for intraoperative fluorescence detection; (3) integrate the miniaturized, flexibleoptical device with endoscopy for minimally invasive detection of tumors; and (4) evaluate the spectralendoscope using spontaneous thoracic tumors in large animals (canines) during surgery to improve diseaseclearance and pathological staging. Accomplishing these specific aims will utilize targeted and activatablenanoparticles to increase specific localization of the probes in cancerous tissue. Detecting and resectingcancerous tissue via the fiber optic endoscopic imaging system will decrease the rate of tumor recurrenceby more accurately detecting surgical margins and residual cancer and reduce surgery associatedmorbidity, such as decreasing patient pain, discomfort, and disability. My immediate career goal is to obtain atenure-track faculty position that focuses on integrating nanotechnology with surgical oncology. Long-term, Iwould like to lead a research program at the interface of science, medicine, and engineering and expand thenumber and types of diseases that will be investigated. Ideally this research would be performed at aninstitution where I can be involved with academic and medical investigators from diverse fields. Training duringthe mentored phase of this award will focus on several key aspects to facilitate my development to achievethese goals as an independent investigator, including (1) providing the candidate with a strong foundation inoptical 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 mentorshipof Dr. Shuming Nie, Ph.D., an international expert in nanotechnology and director of the Emory-Georgia TechCenter for Cancer Nanotechnology Excellence, and at the University of Pennsylvania under the co-mentorshipof Dr. Sunil Singhal, M.D., Director of the Thoracic Surgery Research Laboratory and Chief of ThoracicSurgery. The environment at these two institutions is ideal for this project because I will have full access to themost advanced instrumentation for nanoparticle design, synthesis, and characterization; I will benefit frominstrumentation engineers with fabrication facilities to meet my needs; and a highly collaborative translationalenvironment, which is paramount for successful development of this project that integrates nanotechnologywith minimally invasive intraoperative instrumentation. In addition, the collaborative training will besupplemented by formal coursework at Emory and Georgia Tech in optics and instrumentation.
This career development award seeks to integrate new and innovative nanotechnology methods in cancersurgery. The research performed here will develop methods using nanoparticles to assist surgeons indistinguishing tumor margins and residual tumors while using minimally invasive endoscopic surgery. Thecombined effect of increasing tumor delineation under minimally invasive laparoscopic surgery will have aprofound impact on reducing the high mortality rates from cancer and the morbidity associated with surgery.
