Morphology‐Engineered Bismuth‐Porphyrin MOFs for H 2 S Scavenging Mediated Synergistic Photo‐Immunotherapy Against MRSA‐Infected Diabetic Wounds

Abstract

Diabetic wounds infected with methicillin‐resistant Staphylococcus aureus (MRSA) pose a significant challenge to clinical healing. Proliferating MRSA not only invades neutrophils to induce immunosuppression but also produces hydrogen sulfide (H 2 S) and forms biofilms to enhance its resistance to antimicrobial agents. Herein, three AgTCPP‐BiMOF‐2dDR (PBMD‐1/2/3) particles with cubic, rhombohedral and urchin‐like morphologies are designed as bacteria‐derived H 2 S scavengers to induce N1 neutrophil polarization. Among these morphologies, the formation of heterogeneous structure between urchin‐like PBMD‐3 and in situ produced Bi 2 S 3 enables bandgap modulation, enhancing photodynamic (55.55%, ·OH conversion rate) and photothermal (11.75%) conversion efficiencies under 650/980 nm laser irradiation, respectively. Additionally, more bismuth active sites in the urchin‐like structure significantly boost H 2 S‐scavenging activity, thereby leading to the high expression of the N1 marker CD54 (24.4%). Capitalizing on these merits, urchin‐like PBMD‐3 exhibits the most prominent therapeutic effect, with eradication rates of MRSA and biofilms being nearly 100% in vitro. With catalase (CAT)‐like activity, dual‐metal (Ag/Bi) PBMD‐3 converts endogenous H 2 O 2 into dissolved oxygen to alleviate ROS accumulation and hypoxia. In a MRSA‐infected rat skin wound model, PBMD‐3A hydrogel shows prominent wound healing with negligible systemic toxicity. This work establishes a novel morphology‐dependent immunotherapeutic strategy for the treatment of MRSA‐infected diabetic wounds.