A 2D self-cascade catalytic system based on CoCuFe-LDH nanosheets for accelerated healing of infected wounds.

• The LDH-based cascade catalytic system (CoCuFe-LDH@Gox) is constructed. • The system shows strong POD-like activity and efficient cascade catalytic ability. • It has a high antibacterial effect against drug-resistant bacteria. • It can effectively polarize M2 macrophages to reduce inflammation. • It promotes rapid healing of drug-resistant bacteria-infected wounds. The emergence of drug-resistant bacteria has rendered traditional antibiotics ineffective, posing a serious threat to human health. There is an urgent need to find alternative antimicrobial agents. Inspired by enzyme immobilization and multi-enzyme biocatalysis, we have designed a tri-metal layered double hydroxide (LDHs)-based cascade catalytic system (CoCuFe-LDH@Gox nanosheets) for treating drug-resistant bacterial infections and promoting wound healing. The synergistic effects of the Co, Cu, and Fe in the tri-metal LDHs structure endow CoCuFe-LDH nanosheets with excellent peroxidase (POD)-like activity. The large specific surface area of CoCuFe-LDH nanosheets render them ideal carriers for glucose oxidase (Gox). CoCuFe-LDH@Gox nanosheets can catalyze glucose to produce gluconic acid and H 2 O 2. The generated gluconic acid decreases the local pH, further enhancing the POD-like activity of CoCuFe-LDH@Gox nanosheets at wound site. CoCuFe-LDH@Gox nanosheets can then catalyze H 2 O 2 generating hydroxyl radicals (•OH) to effectively kill drug-resistant bacteria. This synergistic integration of the catalytic LDHs and the Gox components enables the cascade catalytic system to be highly effective against drug-resistant bacteria. In addition to its remarkable antibacterial properties, this LDHs-based system also exhibits excellent biocompatibility and considerable immunomodulatory capabilities. It can accelerate the healing of drug-resistant bacteria-infected wounds by inhibiting the inflammatory response and regulating macrophage polarization. These multifunctional attributes make the CoCuFe-LDH@Gox nanosheets a highly promising candidate for the treatment of drug-resistant bacterial infections in future clinical applications. [ABSTRACT FROM AUTHOR]