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 steadystateangiogenesis imaging and mapping of tumor host response by visualizing internalization of MNP intotumor associated macrophage and/or fibroblasts. Given the clinical data collected over the last severalyears, it is clear that target specific MNP would have significant impact on early cancer detection. Oneapproach to developing novel conjugates is to utilize library and high throughput screening approaches foridentifying the next generation targeted MNP that encompass high stability, reproducible chemistry andoptimized pharmacokineticsThe overall goal of this project is to explore novel synthetic approaches to target MNP to prostate cancer toultimately improve the local detection of this devastating disease. Based on our prior work with completelysynthetic MNP, we will test different library methods and differentially screen thousands of molecules againstknown (hepsin, PAR-1, SPARC, PMSA, PSCA) and yet to be determined prostate cancer targets. The threelibrary approaches, pioneered in our laboratory include small molecule functionalized MNP, novel chimericiron oxide binding peptides (IOBP), and phage display derived binding ligands attached to MNP andoptimized for in vivo imaging. These powerful approaches will enable to us to rapidly screen for imagingagents against a priori known hits as well as novel targets, yet to be established. The project will interactclosely 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 ofthis project is to develop clinically viable nanoparticle platforms for improved detection of cancer by imaging.
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