Bifunctionally-regulated ROS dynamics with sub-nanoscale polyoxometalate cluster functionalized Fe₃O₄ nanozyme for potent infected wound healing

Dynamically modulating the level of reactive oxygen species (ROS) presents a promising strategy for infected wound healing therapy, but conventional approaches predominantly focus on ROS generation, often neglecting the necessity of redox balance. Here we develop a pH-responsive bifunctional nanozyme through coupling sub-nanoscale 12-phosphotungstic acid (PTA) cluster with Fe₃O₄ nanoparticles. This Fe₃O₄-PTA (FPTA) nanozyme can dynamically regulate redox activity within the wound microenvironment: during the early bacterial infection phase of wound niche within acidic pH, it catalyzes the conversion of exogenous H₂O₂ into highly reactive oxygen species, inducing bacterial membrane disruption and apoptosis; while upon restoration of physiological pH during healing phase, it scavenges excess ROS, mitigates inflammation, and promotes re-epithelialization. Catalytic kinetics, evaluated through a double-fitting Michaelis–Menten model, reveals high intrinsic V_max values for H₂O₂ and TMB substrates, and the FPTA nanozyme exhibited potent scavenging capability against ABTS^•, ·OH, and H₂O₂, substantiating its bifunctional catalytic nature. In vitro and in vivo studies demonstrated excellent antibacterial efficacy, biocompatibility, accelerated re-epithelialization, and promoted the infected wound healing, highlighting Fe₃O₄-PTA as an effective bifunctional nanozyme for precise redox modulation in wound care.