Multifunctional Pd Single-Atom Nanozyme for Enhanced Cascade Chemodynamic Therapy of Chronic Wounds

Nanozymes are considered promising therapeutic agents for infected chronic wounds due to their enzyme-like activity-mediated chemodynamic therapy (CDT). However, they still suffer from low catalytic efficiency and incapacity to address excessive glucose and heightened inflammatory responses in chronic wounds. Herein, we bound Pd sites to CeO2 nanosheets in atomically dispersed form by high-temperature calcination, followed by loading glucose oxidase (GOx) to obtain Pd-CeO2@GOx single-atom nanozymes (SANZs) for enhanced cascade CDT of chronic wounds. Specifically, highly endogenous glucose first activates the catalytic activity of GOx for in situ self-supplement of H2O2 and protons. Then, in an acidic microenvironment, the Pd single atoms exert efficient glutathione peroxidase (GSH-Px) mimicking to amplify peroxidase (POD)-mimicking activity, generating burst (OH)-O-center dot to eradicate Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus pathogens and suppress biofilm formation. Finally, Pd sites promote the catalase (CAT)-mimicking activity of CeO2 carriers to convert the remaining H2O2 to O-2, which relieves inflammatory responses and contributes to blood vessel reconstruction in wounds. This cascade CDT strategy by Pd-CeO2@GOx SANZs could accelerate the healing of chronic wounds within 17 days. Therefore, this study opens up insights into the rational design of multienzyme active SANZs for the therapy of chronic wounds.