A gas-liquid biphasic nanocleaner for breaking the self-amplified vicious cycle of barrier disruption-inflammation in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic relapsing disorder primarily driven by the self-amplified vicious cycle of colonic barrier disruption-inflammation (VCBI). Especially, these pathogenic mediators of the VCBI often exist in different phases, such as ROS (inflammatory mediators) in the liquid phase and H 2 S (colonic barrier disruptors) in the gas phase, poses a formidable challenge to their concurrent elimination. Herein, a gas-liquid biphasic nanocleaner (GLBN) is developed for breaking the self-amplified VCBI in IBD by concurrently scavenging the pathogenic factors derived from both liquid and gaseous phases. Benefiting from its high specific surface area, superior intrinsic activity, and ultrasmall size, GLBN provides abundant adsorption and active sites, thereby exhibiting highly efficient H 2 S-capturing capability with a scavenging efficiency of 88.6% and attenuating H 2 S-mediated colonic barrier dysfunction. Meanwhile, owing to its highly efficient ROS-scavenging capacity, with respective scavenging efficiencies of 84.3% for H 2 O 2 and 82.7% for •O 2 - , GLBN effectively suppresses inflammation and promotes macrophage repolarization from the M1 toward the M2 phenotype. Moreover, density function Sal theory (DFT) calculations attribute the biphasic scavenging capabilities to heterogeneous facets and metal-sulfur bonding. Consequently, highly efficient therapy of IBD is achieved in a mouse model. Our study marks a critical breakthrough in the therapeutic application of biphasic scavenging nanozymes for inflammatory diseases triggered by multiphase pathogenic factors.