CT imaging of and therapy for inflammatory bowel disease via low molecular weight dextran coated ceria nanoparticles

Abstract

Inflammatory bowel disease (IBD) affects approximately 3.1 million individuals in the U.S., causing deleterious symptoms such as bloody diarrhea and leading to an increased risk of colorectal cancer. Effective imaging is crucial for diagnosing and managing IBD, as it allows for accurate assessment of disease extent and severity and guides treatment decisions, and monitors therapeutic responses. Computed tomography (CT) with contrast agents is the gold standard for imaging the gastrointestinal tract (GIT). However, current agents are less effective in obese patients and lack specificity for inflamed regions in IBD. Moreover, IBD treatments often have limited efficacy and do not address the role of oxidative stress in IBD progression. This study explores dextran-coated cerium oxide nanoparticles (Dex-CeNP) as a CT contrast agent and therapeutic for IBD, leveraging cerium’s superior K-edge energy profile, inflammation-targeting dextran coating, and cerium oxide’s antioxidant properties. We herein sought to explore the effect of the molecular weight of the dextran coating and therefore synthesized Dex-CeNP formulations using 5, 10, 25, and 40 kDa dextran. In vitro assays showed these formulations to be safe and demonstrated that 5 kDa Dex-CeNP had the highest catalytic activity, which translated into improved suppression of inflammation. This formulation was therefore selected for in vivo use. In vivo CT imaging of mice subjected to dextran sodium sulfate (DSS) colitis showed that Dex-CeNP provided better contrast in the GIT of mice with colitis compared to iopamidol (ISO), with pronounced attenuation in the large intestine and disease- specific retention at 24 hr. Dex-CeNP significantly decreased Disease Activity Index (DAI) scores compared with a currently used drug, indicating that it is effective treatment for colitis. Additionally, Dex-CeNP-treated mice had reduced colon contraction and diminished gastrointestinal bleeding, while being safe and well-excreted. In summary, Dex-CeNP has significant promise as a dual-purpose agent for CT imaging and treatment of IBD.