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

In this study, glucose oxidase (GOx) is mineralized with calcium phosphate (CaP) circled Cu 2 O/Pt nanozyme to form a core–shell structural CuPt-GOx-CaP nanoreactor by a one-step biomimetic mineralization method. The biodegradable and acidity-responsive CuPt-GOx-CaP nanoreactor can be used for starvation and photothermal-enhanced cascade reaction antibacterial therapy. And the release of copper ions have been used for enhanced angiogenesis. • CuPt-GOx-CaP nanoreactor with pH response. • The nanoreactor with starvation/photothermal/chemodynamic therapy. • The nanoreactor depletes Gs and releases O 2 through an enzymatic reaction. • CuPt-GOx-CaP nanoreactor release Cu 2+ and promote angiogenesis. 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 Cu 2 O/Pt nanozyme to form a core–shell structural CaP-GOx-Cu 2 O/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 H 2 O 2 in this reaction is subsequently converted into highly active hydroxyl radicals (•OH) for chemodynamic therapy (CDT) and O 2 for overcoming hypoxia via triple enzyme like activities (peroxidase, oxidase, and catalase) of Cu 2 O/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, Cu 2 O/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.