Targeted oral NGR1@IrOx nanoclusters for synergistic therapy of inflammatory bowel disease

• NGR1@IrO x enables targeted delivery to inflamed colonic tissue, facilitating precision therapy for IBD. • NGR1@IrO x exhibits excellent gastrointestinal stability, resisting degradation in both gastric and intestinal fluids. • NGR1@IrO x achieves dual regulation of oxidative stress and inflammation, offering a synergistic therapeutic strategy for IBD. Inflammatory bowel disease (IBD) remains a clinical challenge due to self-perpetuating cycle of reactive oxygen species (ROS) and chronic inflammation within the pathological microenvironment. In this study, we developed an orally administered nanoclusters by loading notoginsenoside R1 onto iridium oxide nanoclusters (NGR1@IrO x ) to restore intestinal redox balance for improved IBD treatment. The negative surface charge of nanoclusters enables selective accumulation in inflamed colon via electrostatic interactions, overcoming the poor oral bioavailability of NGR1. Moreover, the IrO x core itself exhibits potent ROS-scavenging activity, which acts synergistically with the anti-inflammatory and anti-apoptotic functions of NGR1. In murine DSS-induced colitis models, the NGR1@IrO x nanoclusters outperformed conventional 5-ASA and monotherapies by markedly eliminating ROS, suppressing pro-inflammatory cytokines, inhibiting epithelial apoptosis, and restoring tight junction integrity, ultimately leading to marked mucosal healing. With proven biocompatibility and multimodal efficacy, this work represents a targeted and translatable strategy for IBD management.