(397t) Magnetic Nanoparticles As Multifunctional Carriers for the Diagnosis of Prostate Cancer

Prostate cancer is currently the most common site for cancer in men in the developed world. Despite decades of effort in the fight against cancer, current diagnostic techniques are inaccurate and invasive. Nanoparticles, due to their large surface area and the several functional groups on their surfaces, offer new and exciting opportunities to overcome the shortcomings of conventional diagnostic techniques. We use magnetic iron oxide nanoparticles (MNP) as our multifunctional system due to their intrinsic diagnostic capabilities as MRI contrast agents and the ability to add functionalities, through appropriate surface modifications, to include targeting moieties, fluorescence dyes and radioactive agents. We developed a synthesis method of long-circulating MNPs for sustained tumor exposure that allows for precise control over the physical characteristics of magnetic nanoparticles. Several active targeting strategies will be explored to optimize cancer cell specificity and enhance delivery efficiency based on prostate cancer-specific markers while avoiding nonspecific toxicity to non-tumor sites. Peptide conjugated MNPs will be used to detect proteolytic activity in vivo. Peptides are attractive targeting moieties due to their small size, low immunogenicity and low cost. Phage display techniques will be used to identify peptides capable of detecting Matrix Metalloproteinase (MMP) activity in the tumor site and its microenvironment. The identified peptides will then be optimized through modification of their sequences, and the optimal method of conjugating the peptide to the surface of the MNPs as well as the optimal targeting ligand density will be investigated. The effect of nanoparticle size on biodistribution will also be investigated, using a mouse model, utilizing particles with diameters of 10, 50, 100, and 200 nm.