Developing hyperpolarized silicon particles for advanced biomedical imaging applications

Abstract

Silicon-based nanoparticles are ideally suited as biomedical imaging agents, due to their biocompatibility, biodegradability, and simple surface chemistry that is amenable to drug loading and targeting. A method of hyperpolarizing silicon particles using dynamic nuclear polarization (DNP), which increases magnetic resonance imaging (MRI) signals by 4-5 orders of magnitude through enhanced nuclear spin alignment, has recently been developed and shown viable as a contrast agent for <i>in vivo </i>MRI. Naturally occurring electronic defects on the particle surface obviate the need for exogenous radicals, and the enhanced spin polarization lasts for significantly longer than other hyperpolarized agents (tens of minutes, instead of &lt;1 minute for other species). We report our recent advances in determining the MR characteristics of hyperpolarized silicon particles, which could lead to non-invasive, non-radioactive molecular targeted imaging of various cancer systems. A variety of particle sizes (20 nm-2 μm) were found to have hyperpolarized relaxation times ranging from ~10-50 minutes. The addition of various functional groups to the particle surface, including biocompatible polymers, aptamers, and antibodies had no effect to the hyperpolarization dynamics or relaxation times, and appear to satisfactorily survive the harsh temperature conditions of DNP. Preliminary <i>in vivo </i>studies examined a variety of particle administration routes in mice, including intraperitoneal, tail vein, and rectal injections, as well as oral gavage. Ongoing experiments include targeted molecular imaging in orthotopic murine models of ovarian and colorectal cancers.