Near-Infrared-IIb Fluorescent Nanozymes with Surface Charge Flipping Ability for Imaging-Guided Therapy of Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a common chronic gastrointestinal inflammatory disease with an increasing global incidence. However, a significant challenge in IBD management lies in the coordination between high stability and targeting properties of diagnostic and therapeutic agents. Here, we engineer near-infrared-IIb (NIR-IIb) fluorescent nanozymes with pH-responsive surface charge flipping ability for imaging-guided therapy of IBD. The nanozymes exhibit protonation-induced positive charge (+2.6 mV) in gastric acid for enhanced stability, switching to negative charge (−7.2 mV) in intestinal fluid for targeted accumulation. Therefore, these NIR-IIb fluorescent nanozymes could markedly bypass gastric acid barriers and target damaged colon tissue, revealing a significant NIR-IIb signal in early-stage IBD models versus the control. Meanwhile, Mn doping confers a reactive oxygen species scavenging ability, alleviating inflammation in colitis mice. This dual-functional platform overcomes gastrointestinal barriers, enabling precise lesion targeting and therapy monitoring and offering a promising strategy for personalized IBD management.