A ternary metallic nano-catalytic platform promotes bacterial-infected wound healing via dynamic modulation of ROS

• Ternary metallic nanozyme is prepared by in-situ synthesis and reduction methods. • palladium generate bactericidal hydroxyl radicals first to reduce bacterial biofilm. • CZP nanozymes enable synergistic reactive oxygen species generation and scavenging. • CZP nanozymes promote wound healing via anti-inflammatory and pro-angiogenic effects. Bacterial infections represent a major obstacle in the current clinical treatment of damaged skin. The formation of bacterial biofilm is a significant factor contributing to the development of bacterial drug resistance. Reactive oxygen species (ROS) have anti-biofilm activity whereas the high levels of ROS induce oxidative damage to cells. Herein, ternary metallic nanozymes (CZP nanozymes) were engineered by encapsulating cerium oxide (CeO 2 ) onto zeolitic imidazolate framework-8 (ZIF-8), after which palladium (Pd) was deposited on the surface. The incorporation of Pd imparted the peroxidase-like catalytic properties of the nanozymes, facilitating the generation of bactericidal hydroxyl radicals at the wound site, while the subsequent degradation of ZIF-8 under acidic wound microenvironment facilitated the controlled release of CeO 2 , further eliminating excessive ROS to inhibit inflammation. The hierarchical structure of CZP nanozymes achieved ROS generation and ROS scavenging activities sequentially, enabling the reduction of bacterial biofilm formation and regulating intracellular ROS levels, thereby mitigating oxidative damage. CZP nanozymes could also regulate macrophage polarization and promote angiogenesis while enhancing collagen deposition and re-epithelialization in treated wounds. Therefore, CZP nanozymes hold significant promise as metallic nano-catalytic platforms for the efficient repair of infected wounds by adaptively regulating the ROS balance to achieve antimicrobial and anti-inflammatory effects.