Acidity-responsive cascade nanoreactor based on metal-nanozyme and glucose oxidase combination for starving and photothermal-enhanced chemodynamic antibacterial therapy

Abstract

Persistent inflammation and bacterial infection are common during wound healing, and high blood sugar provides enough nutrients for bacterial growth to make wounds more prone to ulcers. Herein, glucose oxidase (GOx) is mineralized with calcium phosphate (CaP) circled Cu2O/Pt nanozyme to form a core–shell structural CaP-GOx-Cu2O/Pt (GOx-CaPCuPt) nanoreactor. The prepared biodegradable and acidity-responsive GOx-CaPCuPt nanoreactor can be used for near infrared imaging, photothermal enhanced cascade reaction and antibacterial therapy. Oxidation of glucose (Gs) by the GOx can significantly decrease Gs level for starvation therapy, and the generated H2O2 in this reaction is subsequently converted into highly active hydroxyl radicals (•OH) for chemodynamic therapy (CDT) and O2 for overcoming hypoxia via triple enzyme like activities (peroxidase, oxidase, and catalase) of Cu2O/Pt nanozyme. At the same time, the acidic microenvironment due to the generation of gluconic acid will in turn promote the degradation of the GOx-CuCaP nanoreactor and release of copper ions for enhanced angiogenesis. In addition, Cu2O/Pt nanoparticles have strong characteristic absorption in near-infrared region, which can induce a strong photothermal effect (PTT) under the irradiation of 808 nm laser. Under the guidance of near-infrared imaging, the multifunctional nanoreactor can achieve the combination of starvation therapy and PTT-enhanced CDT against Gram-negative and Gram-positive bacteria infectious diseases, which is demonstrated in the staphylococcus aureus infected diabetic rat models.