A CuS-loaded copper-ferrocene framework with synergistic chemodynamic and photothermal antimicrobial therapy for accelerated infected wound healing.

Wound infections pose a critical global health threat, largely exacerbated by biofilm formation and escalating antimicrobial resistance (AMR). This research introduces a novel nanocomposite CCFc that integrates ultrasmall CuS nanoparticles within a copper-based ferrocene-terephthalate metal-organic framework for the promotion of infected wound healing. This elegant design leverages photothermal-enhanced chemodynamic therapy (CDT) and photothermal therapy (PTT) to effectively combat biofilm-related infections and bypass AMR. CCFc exhibits potent peroxidase (POD)-like activity, stemming from both copper and ferrous ions, enabling powerful CDT. Furthermore, copper (II) reacts with reductive glutathione (GSH), enhancing the POD-like activity by forming catalytic Cu(I) sites and intensifying oxidative stress by GSH consume, thereby amplifying CDT efficacy. Under near-infrared (NIR) irradiation, the CuS component provides robust PTT and enhances CDT via localized hyperthermia. The synergistic CDT and PTT results in exceptional in vitro antimicrobial efficacy of CCFc, with a remarkably low minimum bactericidal concentration (MBC) of 6 μg mL-1 against MRSA under NIR irradiation (808 nm, 1.0 W cm-2) and H2O2 (1.0 mM) assistance. Remarkably, CCFc can effectively inhibit both immature biofilm formation and eradicate mature biofilms. In vivo assays demonstrated CCFc's superior antimicrobial and anti-inflammatory properties, thereby significantly accelerating the infected wound healing. With low cytotoxicity and excellent biocompatibility, CCFc shows promising potential for future clinical translation.