Dextran-Coated Cerium Oxide Nanoparticles: A Computed Tomography Contrast Agent for Imaging the Gastrointestinal Tract and Inflammatory Bowel Disease

• Published in: ACS nano 2020-08, Vol.14 (8), p.10187-10197
• Main Authors: Naha, Pratap C, Hsu, Jessica C, Kim, Johoon, Shah, Shrey, Bouché, Mathilde, Si-Mohamed, Salim, Rosario-Berrios, Derick N, Douek, Philippe, Hajfathalian, Maryam, Yasini, Parisa, Singh, Sanjay, Rosen, Mark A, Morgan, Matthew A, Cormode, David P
• Format: Article
• Language: English
• Subjects: Animals; Cerium; Chemical Sciences; Colitis - chemically induced; Colitis - diagnostic imaging; Contrast Media; Dextrans; Inflammatory Bowel Diseases - diagnostic imaging; Inflammatory Bowel Diseases - drug therapy; Medicinal Chemistry; Mice; Nanoparticles
• ISSN: 1936-0851; 1936-086X
• DOI: 10.1021/acsnano.0c03457

Computed tomography (CT) is an X-ray-based medical imaging technique commonly used for noninvasive 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) can produce strong X-ray attenuation due to cerium’s k-edge at 40.4 keV but have not yet been explored for CT imaging. In addition, 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. In this study, therefore, we sought to develop a CT contrast agent, i.e., dextran-coated cerium oxide nanoparticles (Dex-CeNP) for GIT imaging with IBD. We synthesized Dex-CeNP, characterized them using various analytical tools, and examined their in vitro biocompatibility, CT contrast generation, and protective effect against oxidative stress. In vivo CT imaging was done with both healthy mice and a dextran sodium sulfate induced colitis mouse model. Dex-CeNP’s CT contrast generation and accumulation in inflammation sites were compared with iopamidol, an FDA approved CT contrast agent. Dex-CeNP was found to be protective against oxidative damage. Dex-CeNP produced strong CT contrast and accumulated in the colitis area of large intestines. In addition, >97% of oral doses were cleared from the body within 24 h. Therefore, Dex-CeNP can be used as a potential CT contrast agent for imaging GIT with IBD while protecting against oxidative damage.