The special pathological microenvironment of infected wounds (pathology of weakly acidic, hypoxic, and overexpressed H 2 O 2 ) provides fertile soil for the development of disease. Tailoring treatment based on the specific characteristics of the infectious microenvironment (IME) has emerged as a novel direction in the development of antimicrobial therapies. Here, a polyoxovanadate (POV)-based covalent organic polymer (POV-Fc-COP) with inherent photothermal activity was facilely prepared via the copolymerization of 1,1′-bi(3-dimethylamino-1-oxo-2-enylferrocene) (BDOEF) with tris-NH 2 -modified POV (tris-V 6 O 9 ), in which the nanovanadium oxide (V 2 O 3 and V 2 O 5 ) core and polymer shell were generated directly during the Michael addition−elimination reaction. The unique structure and composition impart pH-responsive peroxidase-like (POD-like) and catalase-like (CAT-like) activities, concurrently, to the POV-Fc-COP. Specifically, the acid-activated mimicking-POD activity could consume H 2 O 2 in the microenvironment, producing toxic •OH to combat bacteria and biofilms. The vanadium oxide consumes the excessive acid, resulting in an increase in pH. Meanwhile, the CATlike activity could transform excess H 2 O 2 expression into O 2 to relieve hypoxia induced by the damage of blood vessels in the wounds and facilitate wound healing. Additionally, the synergistic amplified therapeutic effect triggered by the application of laser irradiation facilitates the rapid eradication of bacteria and biofilm, minimizing the detrimental impacts of bacterial proliferation on the IME, thereby accelerating the restoration of the IME return to a normal state. Therefore, POV-Fc-COP with a dual-enzyme functionality could not only utilize but also regulate the IME, significantly expediting the healing of bacteria-infected wounds. This study demonstrates a simple method for the preparation of an intelligent platform for programmed antibacterial and antibiofilm formation, thus promoting healing while utilizing and improving the IME.
