Enzyme-Responsive Nanoemulsions as Tumor-Specific Ultrasound Contrast Agents

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6. PROJECT SUMMARY/ABSTRACT. This proposal supports the application of Dr. Andrew Goodwin for a Pathway to Independence Award in Cancer Nanotechnology (RFA-CA-09-015). Already a promising junior scientist in organic synthesis, macromolecular engineering, and nanotechnology development for cancer imaging and therapy, Dr. Goodwin seeks to obtain training in benchtop and biological validation studies to become a successful independent innovator in cancer nanotechnology. Dr. Goodwin obtained his Ph. D from UC Berkeley in 2007 under the direction of Prof. Jean Fr¿chet, where he designed new polymer architectures and novel release drug mechanisms for cancer therapy. He then continued to the Stanford University CCNE in the labs of Prof. Hongjie Dai, where he functionalized carbon nanotubes and gold nanostructures with new synthetic biocompatible assemblies to create novel hybrid nanostructures with enhanced photophysical properties for in vivo imaging and ex vivo sensors. Currently, he is a Postdoctoral Fellow in the Cancer Therapeutics Training Program at the University of California, San Diego, an NCI- funded T32 program. For the past year, he has been working with Prof. Sadik Esener on developing stimulus-responsive polymer-coated perfluorocarbon microbubbles as ultrasound contrast agents that activate only in regions of inflammation. Already this work has resulted in the filing of a patent and presentation at several conferences. To become a productive independent investigator in cancer nanotechnology, Dr. Goodwin will continue to be mentored by Prof. Sadik Esener, who is a Professor of Electrical and Computer Engineering and Nanoengineering and also the Director of the UCSD Center for Cancer Nanotechnology Excellence (Nanotumor Center). An expert in optical and acoustic detection technologies, Prof. Esener will train Dr. Goodwin in designing instrumentation for evaluation of ultrasound contrast agents and other detection systems. In addition, Prof. Esener will aid Dr. Goodwin in his transition to independence by mentoring him in the preparation and composition of research grants, mentorship of junior scientists, and management of laboratory space and resources. Dr. Goodwin will be co-mentored by Prof. Robert Mattrey, Prof. of Radiology at the Moores Cancer Center and the head of the UCSD In vivo Cancer and Molecular Imaging Center. Prof. Mattrey is an expert in the design, preparation, and clinical evaluation of perfluorocarbon ultrasound contrast agents, and he will train Dr. Goodwin in the design and implementation of biological models to evaluate the clinical efficacy of the proposed contrast agents. This research will be performed at the renowned University of California, San Diego in the Department of Nanoengineering and the Moores Cancer Center, a potent combination for the development of cancer nanotechnology. In his independent work, Dr. Goodwin will adapt the technology he developed at UCSD to create synthetic nanoemulsions that extravasate from circulation and accumulate at the tumor site but only become ultrasound contrast agents after activation by biomarker proteases. Nanoemulsions will be synthesized with a polymer coating that protects the nanoemulsion from vaporization but degrades when exposed to matrix metalloproteinase-2, which is secreted by many cancers. This process will expose ligands that will cause the aggregation and fusion of many nanoemulsions into larger structures, which then spontaneously transform into highly active ultrasound contrast agents during imaging. As the materials are non-toxic and ultrasound is an inexpensive imaging modality, development of this proposal could result in a powerful, safe, and affordable method of cancer imaging and screening. The development of new, promising nanotechnologies for cancer imaging and therapy will require the combination of many different fields of research, from synthesis to electrical engineering to materials science to biology. After receiving training in electrical engineering and animal studies, Dr. Goodwin will be able to design, synthesize, evaluate, and validate new nanomaterial imaging agents solely from his own expertise. With his substantial ability and ambition combined with outstanding mentors and institutional support, Dr. Goodwin is a prime candidate to excel in the independent development of innovative cancer nanotechnologies.