Bifunctionally-regulated ROS dynamics with sub-nanoscale polyoxometalate cluster functionalized Fe 3 O 4 nanozyme for potent infected wound healing

Abstract 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 Vmax 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.