An injectable Ce-MnCo LDH nanozyme gel with cascade catalytic activity for acute radiation proctitis in rats.

Abstract

Acute radiation proctitis (ARP) is a common complication of pelvic radiotherapy driven by direct DNA damage and excessive reactive oxygen species (ROS) induced oxidative stress. Currently, effective clinical treatments that can systematically intervene in ARP are lacking. In this study, we developed an injectable, multicenter cascade nanozyme gel (Ce-MnCo LDH gel) for intrarectal administration to combat radiation-induced intestinal injury. By atomically integrating cerium (Ce) into the lattice of manganese-cobalt layered double hydroxides (MnCo LDH), we constructed a complex multicenter electron transfer network, endowing the nanozyme with potent, broad-spectrum catalase-, superoxide dismutase-, and glutathione peroxidase-like activities that effectively neutralize various ROS. Ce-MnCo LDH gel exhibited good stability and local retention capacity, effectively alleviated radiation-induced oxidative damage, reduced DNA damage, protected mitochondrial function, and inhibited NF-κB-mediated inflammatory signaling. In the ARP rat model, intrarectal administration of Ce-MnCo LDH gel effectively alleviated radiation-induced injury. This platform restored the expression of tight junction proteins (ZO-1 and Claudin-3) in epithelial cells, repaired the integrity of the intestinal epithelial barrier, and remodeled the immune microenvironment in damaged areas by regulating inflammatory factors. In summary, this study provides a promising therapeutic strategy for radiation-induced intestinal injury and other oxidative inflammatory diseases.