Oral phytic acid-coordinated Prussian blue nanozymes reprogram the intestinal microenvironment for effective...

Oral nanozyme therapy is promising for inflammatory bowel disease (IBD), but two issues limit its application: the poor structural and colloidal stability of many nanozymes in the gastrointestinal (GI) tract, and catalytic strategies that address only a single pathological pathway. Phytic acid (PA) was coordinated onto hollow mesoporous Prussian blue nanoparticles (HMPB) in a one-step interfacial reaction to form HMPB-PA. PA coordination increased the hydrodynamic diameter from 144.5 ± 2.4 to 164.4 ± 0.9 nm and shifted the zeta potential from -10.7 ± 0.9 to -23.7 ± 0.3 mV, yielding a negatively charged coordination shell. HMPB-PA retained its number-based hydrodynamic size and most of its catalase (CAT)- and superoxide dismutase (SOD)-like activities in simulated gastric fluid (2 h) and simulated intestinal fluid (36 h). In a dextran sulfate sodium (DSS)-induced colitis model, oral HMPB-PA maintained 97.0% ± 5.1% of baseline body weight (versus 79.9% ± 4.9% for vehicle) and reduced disease activity index and histological damage more effectively than 5-aminosalicylic acid (5-ASA) in this model, while preserving intestinal barrier integrity and microbiota diversity. These results suggest that a single interfacial coordination shell can integrate colloidal stabilization, activity retention, and biological function, offering a physicochemical strategy for gastrointestinally stable oral nanozymes.