Radiation-guided delivery of quantum dot theranostic nanoparticles

Type of Award: Catalyst
Date Awarded: September 2013
Award End Date: August 2015
Amount Awarded: $ 200,000.00
PI(s): Stephen J. Kron, MD, PhD, UChicago; Preston T. Snee, PhD, UIC;

Abstract: The emerging field of "theranostics" (therapeutic diagnostics) has found powerful applications in cancer. Here, a single agent might serve both as a chemotherapy and as a contrast agent to image the tumor and gauge the effects of therapy. Recent advances have been in engineering nanomaterials to combine an imaging probe with the capacity to deliver a molecular payload. The Kron lab at UC hopes to apply theranostics to radiotherapy (RT), using imaging to improve treatment planning and to improve outcomes by the delivery of radiosensitizers. They hope to exploit the newly described radiation-enhanced permeability and retention (R-EPR) effect. Here, radiation disrupts the endothelial barrier between the bloodstream and tumor, permitting macromolecules and nanoparticles to flow in. This discovery has sparked a new collaboration with the Snee group at UIC, pioneers in fluorescent quantum dot (QD) chemistry, aimed at developing novel imaging and drug delivery agents. While QDs are bright and stable nanoparticle fluorophores, the complexity of synthesis and functionalization has prevented their broad applications in biology. Snee has developed novel chemistry to achieve high solubility and stability as well as to coat QDs with drugs and DNA. For this project, Snee will develop synthetic methods to produce near-infrared (NIR) fluorescent QDs, allowing their detection within living mice, and to coat the QDs so they circulate freely in the blood while carrying payloads such as chemotherapy drugs or gene therapies. Kron will then optimize R-EPR delivery of these QD theranostic agents, using imaging to follow the accumulation of QDs in the tumor and to monitor the effects on tumor responses to radiation. Demonstrating the ability to target and eliminate tumors with radiation- guided nanoparticle theranostics can be rapidly translated to significantly improve the value of radiosurgery for cancer.