MRI-visible CDDO-Me@AL/HA hydrogel for theranostics of radiation-induced intestinal injury

Radiation-induced intestinal injury (RIII) is a serious complication of abdominal and pelvic radiotherapy. Its mechanism is complex, and traditional treatment methods are difficult to achieve precise intervention and efficacy visualization. Bardoxolone methyl (CDDO-Me) has a therapeutic effect on intestinal injury as an Nrf2 activator. However, there are limitations such as uncontrolled drug release and lack of efficacy visualization. To address this problem, we prepared a sodium alginate/hyaluronic acid (AL/HA) pH-responsive oral hydrogel loaded with CDDO-Me, and introduced melanin nanoparticles (SMNP) with enhanced MRI signal to achieve non-invasive visualization of the distribution, localization and retention of the hydrogel in rats. The hydrogel exhibited resistance to gastric acid, mucoadhesive properties, and prolonged retention in the small intestine and colon, thus achieving controlled intestinal release of drugs. In addition, our research suggested that the oral CDDO-Me@AL/HA@SMNP hydrogel could alleviate intestinal oxidative stress injury and down-regulate pro-inflammatory cytokines in mouse models. These effects may be associated with Nrf2 activation and ROS clearance, and may also involve the PI3K/Akt/GSK3β pathway. Overall, our research indicated that the CDDO-Me@AL/HA@SMNP hydrogel integrates therapeutic efficacy with MRI-based visualization/tracking capabilities for RIII. These findings represent a preclinical proof-of-concept, and further optimization, safety evaluation, and translational studies are required before any potential clinical application.