Near-Infrared-Controlled Nanoplatform Exploiting Photothermal Promotion of Peroxidase-like and OXD-like Activities for Potent Antibacterial and Anti-biofilm Therapies

Abstract

Nanozymes that mimic peroxidase (POD) activity can convert H₂O₂ into bactericidal free radicals, which is referred to as chemodynamic therapy (CDT). High glutathione (GSH) levels in the infectious tissue severely limit the performance of CDT. Herein, we report a near-infrared-controlled antibacterial nanoplatform that is based on encapsulating tungsten sulfide quantum dots (WS₂QDs) and the antibiotic vancomycin in a thermal-sensitive liposome. The system exploits the photothermal sensitivity of the WS₂QDs to achieve selective liposome rupture for the targeted drug delivery. We determined that WS₂QDs show a strong POD-like activity under physiological conditions and the oxidase-like activity, which can oxidate GSH to further improve the CDT efficacy. Moreover, we found that increased temperature promotes multiple enzyme-mimicking activities of WS₂QDs. This platform exerts antibacterial effects against Gram-positive Mu50 (a vancomycin-intermediate <i>Staphylococcus aureus</i> reference strain) and Gram-negative <i>Escherichia coli</i> and disrupts biofilms for improved penetration of therapeutic agents inside biofilms. <i>In vivo</i> studies with mice bearing Mu50-caused skin abscess revealed that this platform confers potent antibacterial activity without obvious toxicity. Accordingly, our work illustrates that the photothermal and nanozyme properties of WS₂QDs can be deployed alongside a conventional therapeutic to achieve synergistic chemodynamic/photothermal/pharmaco therapy for powerful antibacterial effects.