Aptamer and DNAzyme-Functionalized Cu-MOF Hybrid Nanozymes for the Monitoring and Management of Bacteria-Infected Wounds

Metal-organic frameworks (MOFs) with peroxidase (POD)-like activity have great potential for combating drug-resistant bacterial infections. However, the use of POD-like activities is severely limited by low oxygen levels and high levels of glutathione (GSH) within the microenvironment of bacterial infection. Herein, G-quadruplex/hemin DNAzyme-aptamer probes and tannic acid-chelated Au nanoparticle (Au-TA)-decorated Cu-based MOF nanosheets (termed GATC) with triple-enzyme activities were developed for visual detection and efficient antibacterial therapy. First, the monometallic MOFs (Cu-ZIF) showed the best catalytic and loading capacity performance compared with the bimetallic MOFs (CoCu-ZIF and ZnCu-ZIF). Then, Cu-MOFs, Au-TA, and DNAzyme improve the POD-like activity to generate more hydroxyl radicals (•OH) to kill bacteria. GATC can bind to bacteria through aptamer recognition, increasing the bacterial surface contact area for efficient antibacterial activity. GATC can decompose H2O2 into O2 to alleviate hypoxia and improve the microenvironment due to its catalase (CAT)-like activity. In addition, GATC exhibited GSH peroxidase-like activity, which can avoid the loss of •OH and result in bacterial death more easily. Compared with previous studies, GATC exhibited extraordinary bactericidal ability at an extremely low dosage of 3 μg/mL against methicillin-resistant Staphylococcus aureus (MRSA). Notably, the GATC-catalyzed chromogenic reaction could accurately monitor the MRSA infection treatment process. Overall, this work could establish a therapeutic platform for the monitoring and management of bacteria-infected wounds.