pH-Responsive Oxygen and Hydrogen Peroxide Self-Supplying Nanosystem for Photodynamic and Chemodynamic Therapy of Wound Infection

Abstract

The combination of photodynamic therapy (PDT) and chemodynamic therapy (CDT) has been continuously explored in the antibacterial aspect and has achieved more effective antibacterial effect than a single therapy. We design a pH-responsive O₂ and H₂O₂ self-supplying zeolitic imidazolate framework-67 (ZIF-67) nanosystem for PDT/CDT of wound infection. Under the acidic inflammatory conditions, ZIF-67 can degrade to produce Co²⁺ and release CaO₂ and graphene quantum dots (GQDs). The exposed CaO₂ reacted with water to generate H₂O₂ and O₂. The self-supplied O₂ alleviates hypoxia at the site of inflammation and enhances external light-initiated GQD-mediated PDT, while H₂O₂ was catalyzed by endogenous Co²⁺ to produce hydroxyl radicals for Co²⁺-triggered CDT. <i>In vitro</i> and <i>in vivo</i> experiments confirm that CaO₂/GQDs@ZIF-67 has a combined PDT/CDT effect. The antibacterial mechanism indicates that bacteria post-treated with CaO₂/GQDs@ZIF-67 may be sterilized by reactive oxygen species-mediated oxidative stress and the leakage of bacterial contents. The experiments also find that CaO₂/GQDs@ZIF-67 may activate the immune response and enhance the therapeutic effect by activating the cyclic GMP-AMP synthase-stimulator of interferon genes signaling pathway.