Cerium oxide nanoparticles for CT imaging and catalytic therapeutic intervention in inflammatory bowel disease

University Of Pennsylvania, Philadelphia PA

Investigators

Abstract

PROJECT SUMMARY Computed tomography (CT) is an x-ray based medical imaging technique commonly used for non-invasive gastrointestinal tract (GIT) imaging. Iodine and barium based CT contrast agents are used in the clinic for GIT imaging, however, inflammatory bowel disease (IBD) imaging is challenging since iodinated and barium based CT agents are not specific for sites of inflammation. Cerium oxide nanoparticles (CeNP) produce strong x-ray attenuation due to cerium's k-edge at 40.6 keV, but have only recently begun to be explored for CT imaging. We hypothesized that the use of dextran as a coating material on cerium oxide nanoparticles would encourage accumulation in IBD inflammation sites in a similar fashion to other inflammatory diseases. We have therefore studied a novel CT contrast agent, i.e. dextran coated cerium oxide nanoparticles (Dex-CeNP) for imaging GIT with IBD. Dex-CeNP produced strong CT contrast and accumulated in the IBD area of large intestines. >97 % of oral doses (an exceptionally high value) were cleared from the body within 24 hrs and the agents were found to be safe from clinical blood chemistry measurements and histology. Moreover, current treatments for IBD have poor efficacy and lead to undesirable side effects. Cerium oxide nanoparticles have significant anti-inflammatory properties, as indicated by our preliminary data. We therefore also hypothesized that Dex-CeNP may prove to be an effective treatment for IBD. We herein propose to develop several variations of Dex-CeNP characterize them, test them for their potential for imaging IBD and as a novel therapeutic for this disease, as well as perform extensive safety testing. By assembling a complementary team of scientists and physicians at the University of Pennsylvania, we seek to develop a breakthrough imaging and therapeutic agent for IBD.