Dextran coated magnetic nanoparticles (MNP) have become important tools for clinical cancer imaging, highly improving the accuracy of clinical staging. The same materials have also been shown to allow steadystate angiogenesis imaging and mapping of tumor host response by visualizing internalization of MNP into tumor associated macrophage and/or fibroblasts. Given the clinical data collected over the last several years, it is clear that target specific MNP would have significant impact on early cancer detection. One approach to developing novel conjugates is to utilize library and high throughput screening approaches for identifying the next generation targeted MNP that encompass high stability, reproducible chemistry and optimized pharmacokinetics The overall goal of this project is to explore novel synthetic approaches to target MNP to prostate cancer to ultimately improve the local detection of this devastating disease. Based on our prior work with completely synthetic MNP, we will test different library methods and differentially screen thousands of molecules against known (hepsin, PAR-1, SPARC, PMSA, PSCA) and yet to be determined prostate cancer targets. The three library approaches, pioneered in our laboratory include small molecule functionalized MNP, novel chimeric iron oxide binding peptides (IOBP), and phage display derived binding ligands attached to MNP and optimized for in vivo imaging. These powerful approaches will enable to us to rapidly screen for imaging agents against a priori known hits as well as novel targets, yet to be established. The project will interact closely with the Schreiber lab in small molecule diversity, with the Belcher lab for binding peptide screens, with the Langer lab for optimizing delivery and with the Rubin lab for target identification. The ultimate goal of this project is to develop clinically viable nanoparticle platforms for improved detection of cancer by imaging.
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