Triple-Enzyme Mimetic Flexible-Interlaced Ferromagnetic Porous-Organic-Polymer for Self-Adaptive Antibacterial Cascade Therapy via Microenvironment-Reprogramming and Photosensitizer-Aggregation-Suppression

The complex pathological microenvironment of infected wounds impedes antimicrobial efficacy while accelerating bacterial resistance. To overcome this, an oxygen-evolving polyphenol-based magnetic porous polymer (FcPor-POP) was engineered through the covalent conjugation of ferrocene-derived enzymatic units and photoactive polyphenol-porphyrin via phenolic-aldehyde condensation. The concurrently introducing antiquenching structural motifs, realized by flexible saturated carbon linkages, sandwich-like interleaved units, as well as a hydrogen-bond interlocked structure, effectively suppress photoactivity loss induced by π–π aggregation. The FcPor-POP system achieves adaptive antibacterial action through hierarchically coordinated spatiotemporal mechanisms. Pathological microenvironmental cues dynamically trigger enzymatic activity switching. Under acidic pH, the ferrocene units and in situ-formed Fe3O4 nanoparticles exhibit peroxidase-like (POD) activity, converting H2O2 to cytotoxic •OH (accelerated by photothermal heating). Upon H2O2 depletion, oxidase-like (OXD) activity dominates, leveraging multivalent iron centers to produce O2•–, preserving enzyme-like antibacterial function. Targeted ROS delivery is enabled by phenolic hydroxyl groups that anchor to bacterial membranes via H-bonding, combined with rough surface topography enhancing physical adhesion. This minimizes the distance between ROS generation sites (Fe centers/photosensitizers) and bacterial targets, ensuring efficient membrane disruption by short-lived species. The polymer matrix orchestrates three cross-amplifying circuits. The catalase-like (CAT) activity decomposes H2O2 into O2, alleviating hypoxia while fueling the OXD and photodynamic therapy (PDT) in a self-reinforcing cycle. Photothermal cascades amplify all enzyme kinetics (POD/OXD/CAT) and directly damage pathogens. Microenvironment reprogramming occurs as in situ-formed Fe3O4 consumes H+/H2O2, elevating local pH to disrupt bacterial acid tolerance and reduce oxidative stress. This hierarchical coordination, where microenvironment sensing controls temporal enzyme switching, membrane targeting enables spatial ROS precision, and light-driven cascades (O2 self-supply, PDT, PTT activation, and multienzyme synergy) optimize material/energy flow, establishes FcPor-POP as a dynamic therapeutic system with maximal antibacterial efficacy.