Hybrid therapeutic agents for self-oxygenating wound therapy via infectious microenvironment modulation

Artificial enzymes mimicking natural processes offer promising solutions for treating infections, but their development faces challenges in synthesis complexity and therapeutic performance. We present a modular-assembly strategy to construct hierarchical MOF@COF heterostructures through covalent interface engineering, bypassing the need for function-specific monomer synthesis while amplifying functionality. By growing porphyrin-based COF shell on amino-functionalized Fe-MIL-88A MOF core, we achieved a morphology-controlled core-shell architecture with well-defined heterojunctions. This hybrid integrates the MOF's dual peroxidase- and catalase-like activities with the COF's photoactivity, enabling cascade therapeutic effects. MOF@COF selectively converts endogenous H₂O₂ into bactericidal ⋅OH and O₂ within infected tissues, enhancing photodynamic therapy through improved light harvesting and charge separation while alleviating hypoxia-induced resistance. As a broad-spectrum antimicrobial agent, MOF@COF simultaneously utilizes and remodels the infectious microenvironment, significantly accelerating wound healing. This work demonstrates a rational design approach for biocompatible artificial enzymes with synergistic catalytic sites, advancing self-reinforcing therapeutic strategies for infection treatment.