An AB-Type Hydrogel CT Contrast Agent for Precise Localization of Intra-Abdominal Hemorrhage

Intra-abdominal hemorrhage is a life-threatening condition with high mortality. Rapid localization of the bleeding point is crucial. Conventional computed tomography (CT) imaging is limited by the rapid diffusion and poor retention of small-molecule iodine agents, restricting sensitivity and imaging duration. To overcome these challenges, an “AB-type” hydrogel CT contrast system is developed based on bio-orthogonal click chemistry, designed to enhance both detection sensitivity and spatial precision. The system consists of iodized oil-loaded liposomal nanoparticles (INb NPs) administered intravenously and tetrazine-functionalized hyaluronic acid (HA-Tz) delivered intraperitoneally. At the bleeding site, the two components undergo a rapid click reaction, forming an in situ hydrogel that anchors the contrast agent for prolonged retention and precise localization. This approach demonstrated efficient gelation in vitro and robust performance in vivo, significantly extending the imaging window and sensitivity compared with Iohexol. HA-Tz@INb NPs enhance CT signal intensity and imaging duration by over 60 fold, enabling sensitive detection of occult bleeding. The hydrogel exhibits excellent biosafety, being removable by lavage and fully degradable within days without adverse effects. By integrating nanotechnology, click chemistry, and hydrogel engineering, this strategy provides a clinically translatable diagnostic platform with superior precision and sensitivity for intra-abdominal bleeding.