NIR-controlled photothermal intelligent nanozyme synergizes catalysis and gas therapy for multidimensional treatment of inflammatory bowel disease.

The vicious feedback loop between reactive oxygen species (ROS)-triggered mucosal inflammation and intestinal epithelial barrier disruption represents a critical mechanism driving the onset and progression of inflammatory bowel disease (IBD). Traditional nanozymes primarily focus on scavenging ROS to suppress excessive immune responses, but generally lack intrinsic functionality for direct intestinal barrier restoration. Given the substantial potential of mild photothermal effects and nitric oxide (NO) gas in restoring barrier integrity, we engineered a near-infrared (NIR)-controlled photothermal intelligent nanozyme (FU/PBN@CUR) by loading curcumin (CUR) into NO donor-doped Prussian blue nanozymes (PBN), which were further encapsulated within a pH-responsive fucoidan/chitosan (FU/CS) hydrogel. In cytological and pharmacodynamic studies, the P-selectin-targeting and pH-responsive properties of FU/CS hydrogel remarkably enhanced FU/PBN@CUR accumulation in inflamed colon. The intrinsic enzymatic activity of the PBN effectively scavenged ROS in macrophages, driving their phenotypic conversion from the M1 to the M2 subtype. Notably, NIR triggered hyperthermia-induced autophagy and NO release from PBN, which synergistically promoted intestinal epithelial cell proliferation and tight junction protein expression, thereby restoring the integrity of the intestinal epithelial barrier. Collectively, our designed nanoplatform synergistically accomplished ROS elimination-autophagy activation-NO gas delivery behaviors, providing a novel "one stone, three birds" therapeutic strategy for IBD treatment.