In Situ-Forming Bioresponsive Liposome-Anchored Hydrogel Restores Redox-Immune Homeostasis in Mucosal Macrophages for Radiation-Induced Rectal Injury Repair

Herein, we identify that the redox-immune dyshomeostasis of mucosal macrophages as a major pathological driver of RRI-associated acute inflammation and chronic fibrosis and developed an in situ forming reactive oxygen species (ROS)-responsive liposome-anchored hydrogel (Lip@H151@TK-PF127 Gel) for effective RRI repair.

For this purpose, liposomes were further grafted with mannose moieties via thioketal (TK) linkers for loading cGAS-STING inhibitor H151, which were further conjugated onto the TK-PF127 Gel. The Lip@H151@TK-PF127 Gel precursors could be facilely administered to the RRI site via enema and undergo temperature transition to achieve in situ gelation, which would be subsequently activated by local ROS to trigger Lip-TK-Man@H151 release.