Integrating Artificial DNAzymes with Natural Enzymes on 2D MOF Hybrid Nanozymes for Enhanced Treatment of Bacteria‐Infected Wounds

Removal of invasive bacteria is critical for proper wound healing. This task is challenging because these bacteria can trigger intense oxidative stress and gradually develop antibiotic resistance. Here, the use of a multienzyme-integrated nanocatalytic platform is reported for efficient bacterial clearance and mitigation of inflammatory responses, constructed by physically adsorbing natural superoxide dismutase (SOD), in situ reduction of gold nanoparticles (Au NPs), and incorporation of a DNAzyme on 2D NiCoCu metal-organic frameworks (DNAzyme/SOD/Au@NiCoCu MOFs, termed DSAM), which can adapt to infected wounds. O2 and H2 O2 replenishment is achieved and alleviated the hypoxic microenvironment using the antioxidant properties of SOD. The H2 O2 produced during the reaction is decomposed by peroxidase (POD)-like activity enhanced by Au NPs and DNAzyme, releasing highly toxic hydroxyl radicals (•OH) to kill the bacteria. In addition, it possesses glutathione peroxidase (GPx)-like activity, which depletes GSH and prevents •OH loss. Systematic antimicrobial tests are performed against bacteria using this multienzyme-integrated nanoplatform. A dual-mode strategy involving natural enzyme-enhanced antioxidant capacity and artificial enzyme-enhanced •OH release to develop an efficient and novel enzyme-integrated therapeutic platform is integrated.