Hybrid Nanoparticles in Imaging and Therapy of Prostate*

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DESCRIPTION (provided by applicant): The University of Missouri (MU) Cancer Nanotechnology Platform (CNP) is the culmination of long-standing interdisciplinary partnerships in departments within the School of Medicine, the College of Arts and Science, the College of Veterinary Medicine, the Ellis Fischel Cancer Center, the Missouri University Research Reactor and the College of Engineering. Our CNP's overarching goal focuses on developing hybrid gold nanoparticle-based molecular imaging agents and targeted therapeutic agents that are effective in the diagnosis and treatment of prostate cancer. The specific objectives of our CNP include the following: (i) Synthesize and use a library of gold nanoparticles (AuNPs) for conjugation with prostate tumor-specific bombesin peptides. Investigate the photophysical properties, dispersity, and size-dimension measurements on these gold nanoparticles. (ii) Investigate biolocalization, pharmacokinetics and in vivo profiles of AuNPs stabilized with starch, agarose, and arabinagalactan protein (gum Arabic) in pigs. We will optimize analytical protocols, using techniques of neutron activation analysis (NAA), atomic absorption and radiochemical analysis using Au-198 nanoparticulate tracer, for the accurate estimation of AuNPs/gold metal in tissues and biological fluids, (iii) Develop new theoretical models, computations and simulations for the interaction of AuNPs with cells, (iv) Investigate the utility of AuNPs and bombesin-conjugated hybrid AuNPs as image enhancers in computed tomographic (CT) and ultrasound (US) imaging of prostate tumors in SCID mice implanted with human prostate cancer xenografts and with experimental modeling, simulations and studies on anthropomorphic phantom models of prostate cancer, (v) Optimize production of nanoparticulate a-emitting Au-198/199 and their utility for designing and developing tumor-specific Au-198/199-nanoparticlelabeled bombesin peptides for prostate tumor therapy. These studies will validate that multiple atoms of fiemitting Au-198 isotope, characteristic of nanoparticulate gold, will deliver significantly higher therapeutic payload to tumor sites than any conventional therapy. The MU Nanoparticles Production Core Facility will serve as a research and production resource for the unhindered supply of AuNPs to all investigators within the CNP program. The CNP provides unique opportunities for professionals from diverse academic backgrounds to be involved in collaborative scientific interactions that further our interdisciplinary research, education and product development program. We will apply principles of nanoscience and nanotechnology to develop innovative molecular imaging and therapeutic approaches to combat prostate cancer.