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 severity, 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 associated with 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, dextran's inflammation-specific targeting, and cerium oxide's antioxidant properties. Herein, we synthesized Dex-CeNP formulations using 5, 10, 25, and 40 kDa dextran to explore the effect of dextran coating molecular weight. In vitro assays showed formulation biocompatibility and demonstrated that 5 kDa Dex-CeNP had the highest catalytic activity, which translated into improved suppression of inflammation. As a result, this formulation was 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 h. Additionally, Dex-CeNP significantly decreased Disease Activity Index (DAI) scores, and diminished gastrointestinal bleeding when compared with a currently approved drug, indicating that it is an effective treatment for colitis. Studies also revealed that the Dex-CeNPs were safe and well-excreted following administration. In summary, Dex-CeNP has significant promise as a dual-purpose agent for CT imaging and treatment of IBD.