Spectral Computed Tomography Diagnosis of Inflammatory Bowel Disease with Neodymium-Hyaluronic Acid Nanoparticles

Early detection and nonintrusive assessment of inflammatory bowel disease (IBD) remain an unmet clinical challenge. Spectral computed tomography (CT) presents a potential modality for gastrointestinal (GI) imaging; however, clinical CT contrast agents are unable to achieve targeted detection of IBD in spectral CT imaging. In this study, we developed neodymium-hyaluronic acid nanoparticles (Nd-HA NPs) as novel contrast agents for spectral CT imaging of IBD. Nd-HA NPs were synthesized by conjugating HA units with lanthanide complex neodymium-diethylenetriamine-pentaacetic acid (Nd-DTPA). The physical properties, biotoxicity, and CT imaging ability of Nd-HA NPs were systematically evaluated in vitro. Subsequently, the applicability of Nd-HA NPs for GI tract imaging was assessed in both healthy and colitis mouse models. Nd-HA NPs exhibited excellent stability, biocompatibility, and potent x-ray attenuation property in vitro as novel spectral CT contrast agents. Attributed to HA's high affinity for cluster of differentiation 44 receptor, which is abundantly expressed at inflammatory sites, Nd-HA NPs successfully achieved targeted spectral CT imaging of IBD, and showed greater accumulation in the lesions of colitis mice compared with the clinical contrast agent iohexol. More importantly, after oral administration of Nd-HA NPs, the CT values of GI tract in healthy mice, 2.5% DSS-induced mice (moderate colitis), and 5% DSS-induced mice (severe colitis) were 90.19, 140.99, and 264.07 HU, respectively, with statistically significant difference (<i>P</i> < 0.001). These results indicated that Nd-HA NPs had the potential to realize severity assessment of IBD in spectral CT imaging, which was further confirmed by inductively coupled plasma optical emission spectrometry analysis and histopathological evaluation. The study suggested that Nd-HA NPs could serve as effective spectral CT contrast agents, enabling noninvasive early detection and severity assessment of IBD.