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

Abstract

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.

Biomedical Applications of Iron Oxide Nanoparticles: Current Insights Progress and Perspectives

“…This involves capping SPIONs with organic acids (citric acid [42] and oleic acid [43,44]) or coating them with biocompatible hydrophilic polymers (poly(ethylene glycol) (PEG) [45][46][47][48][49] poly(vinyl alcohol) (PVA) [50,51], polyvinyl pyrrolidine (PVP) [52], polysaccharides, such as chitosan or dextran [53][54][55][56], while noncoated SPIONs have a tendency to aggregate in the bloodstream after intravenous injection. PEG-SPIONs show prolonged half-life time of SPIONs and reduce their cellular uptake.…”

“…Magnetite was combined with bismuth to achieve dual MRI-CT contrast agents [56]. Several studies refer to iron oxide-based hybrid nanoparticles for MRI-CT that combine the magnetic compound with gold.…”

Redox-active nanoparticles for inflammatory bowel disease

“…3(b)) [79]. Naha et al developed biocompatible dextran-coated CeO2 NPs that could preferentially accumulate in colonic inflamed sites and protect cells against oxidative stress, and that could also act as CT contrast agents due to strong X-ray attenuating capacity [80]. Et et al proved that Eu-doped CeO2 NPs could effectively eliminate O2  and relieve intestinal ischemiareperfusion injury [66].…”

Recent Progress in the Diagnosis and Precise Nanocarrier-Mediated Therapy of Inflammatory Bowel Disease

“…Naha et al designed and synthesized nanocontrast agents that can be used in the diagnosis and treatment of IBD, which were named dextran-coated cerium oxide nanoparticles (Dex-CeNPs). 124 This nanocontrast agent consists of a cerium oxide core and a dextran shell, which can endow the system with strong CT contrast due to the higher k-edge of cerium oxide and the stability, biocompatibility, and specificity in the inflammation sites due to the unique physicochemical properties of dextran. 125 , 126 Furthermore, cerium oxide can act as an artificial ROS scavenger 127 to reduce the high oxidative stress in intestinal lesions to alleviate inflammation.…”