A multifunctional cascade nanoreactor based on Fe-driven carbon nanozymes for synergistic photothermal/chemodynamic antibacterial therapy

Healing bacterial chronic wounds caused by hyperglycemia is of great significance to protect the physical and mental health of diabetic patients. In this context, emerging chemodynamic therapy (CDT) and photothermal therapy (PTT) with broad antibacterial spectra and high spatiotemporal controllability have flourished. However, CDT was challenged by the near-neutral pH and inadequate H2O2 surrounding the chronic wound site, while PTT showed overheating-triggered side effects (e.g., damaging the normal tissue) and poor effects on thermotolerant bacterial biofilms. Therefore, we engineered an all-in-one glucose-responsive photothermal nanozyme, GOX/MPDA/Fe@CDs, consisting of glucose oxidase (GOX), Fe-doped carbon dots (Fe@CDs), and mesoporous polydopamine (MPDA), to efficiently treat chronic diabetic wound bacterial infections and eradicate biofilms without impacting the surrounding normal tissues. Specifically, GOX/MPDA/Fe@CDs produced a local temperature (∼ 45.0°C) to enhance the permeability of the pathogenic bacterium and its biofilm upon near-infrared (NIR) 808 nm laser irradiation, which was seized to initiate endogenous high blood glucose to activate the catalytic activity of GOX on the GOX/MPDA/Fe@CD surface to achieve the simultaneous self-supplying of H2O2 and H+, cascade catalyzing •OH production via a subsequent peroxidase-mimetic activity-induced Fenton/Fenton-like reaction. As such, the in vivo diabetic wound infected with methicillin-resistant Staphylococcus aureus was effectively healed after 12.0 days of treatment. This work was expected to provide an innovative approach to the clinical treatment of bacterially infected diabetic chronic wounds. STATEMENT OF SIGNIFICANCE: An all-in-one glucose-responsive photothermal nanozyme GOX/MPDA/Fe@CDs was constructed. Cascade nanozyme GOX/MPDA/Fe@CDs self-supply H2O2 and H+ to break H2O2 and pH limits to fight bacterial infections. Synergistic chemotherapy and photothermal therapy with nanozyme GOX/MPDA/Fe@CDs accelerates healing of biofilm-infected diabetic wounds.