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HARVARD COLLEGE, PRESIDENT & FELLOWS OF

The overall goal of the proposed research is to functionalize Si nanoparticles to target common cancers, enhance the nuclear magnetic resonance (NMR) signal of these particles using dynamic nuclear polarization (DNP), and characterize the hyperpolarized particles in vitro. These are vital steps toward our overall objective of developing a novel molecular imaging probe based on Magnetic Resonance Imaging of hyperpolarized silicon nanoparticles, to provide a novel tool for measuring and imaging biological processes in health and disease. The use of hyperpolarized noble gases for lung imaging has clearly demonstrated the benefits of imaging hyperpolarized agents, providing both dramatically increased detection sensitivity as well as eliminating all background signals. Recently, 13C imaging of 13C-hyperpolarized metabolites has provided a method for rapid metabolic profiling. However, the very short nuclear relaxation times of hyperpolarized agents used, typically less than 60 s for most 13C agents, is much too short for the imaging of targeted molecular probes that require several hours to both reach and bind their targets. The investigators have demonstrated that Si nanoparticles can be surface-coated, have their polarization enhanced by over three of orders of magnitude compared to room temperature Boltzmann polarization, and that the 29Si nanoparticle spins can exhibit nuclear relaxation times >500 s. Investigators have also shown that this relaxation time can be tailored for the application by modifying particle size. The present proposal focuses on functionalization of the nanoparticles to target common cancer cells and efforts to maximize and retain the hyperpolarization of the Si nanoparticles during delivery. Such 29Sibased imaging agents will provide powerful and much needed new tools for targeted molecular imaging, cell tracking and the detection of tumors. The proposal consists of three specific aims. The first aim is to develop targetable Si nanoparticles that can be hyperpolarized; the second aim is to develop high efficiency dynamic nuclear polarization; the third aim is to perform standard NMR and MRI on the functionalized nanoparticles, before and after hyperpolarization.

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