Aptamer-Functionalized DNA Tetrahedra Loading GOx/HRP Cascade System for Targeted Therapy of Infected Wounds

The skin serves as the primary barrier for human health, yet its integrity is frequently compromised by environmental stressors, leading to wounds where bacterial infection poses a significant clinical obstacle. To address escalating antibiotic resistance and the biocompatibility issues of exogenous antibacterial agents, this project developed an intelligent targeted recognition and efficient antibacterial system (Th^A-GH) based on endogenous biocomponents. Leveraging the exceptional spatial addressability and structural programmability of DNA tetrahedra (Th), we integrated bacteria-specific aptamers via edge hybridization and precisely colocalized glucose oxidase (GOx) and horseradish peroxidase (HRP) within the Th nanocavity using extended DNA capture strands. The system mimics natural compartmentalized intracellular environments, significantly enhancing GOx/HRP cascade efficiency through spatial confinement. Th^A-GH specifically recognizes and anchors onto bacterial surfaces, where it depletes localized glucose to sever nutrient supply and simultaneously generates highly reactive hydroxyl radicals (·OH) to disrupt bacterial membranes in situ. Experimental data demonstrate that Th^A-GH exhibits potent antibacterial activity against both Gram-positive and Gram-negative bacteria in vitro and effectively accelerates the healing of infected wounds in vivo. This study underscores the potential of DNA nanotechnology for precise enzyme regulation, offering a high-efficiency, biocompatible, and targeted non-antibiotic strategy for clinical wound management.