A Biofilm Microenvironment‐Activated Single‐Atom Iron Nanozyme with NIR‐Controllable Nanocatalytic Activities for Synergetic Bacteria‐Infected Wound Therapy

Abstract Biofilm microenvironment (BME)‐activated antimicrobial agents display great potential for improved biofilm‐related infection therapy because of their superior specificities and sensitivities, effective eliminations, and minimal side effects. Herein, BME‐activated Fe‐doped polydiaminopyridine nanofusiform‐mediated single‐atom nanozyme (FePN SAzyme) is presented for photothermal/chemodynamic synergetic bacteria‐infected wound therapy. The photothermal therapy (PTT) function of SAzyme can be specifically initiated by the high level of H 2 O 2 and further accelerated through mild acid within the inflammatory environment through “two‐step rocket launching‐like” process. Additionally, the enhanced chemodynamic therapy (CDT) for the FePN SAzyme can also be endowed by producing hydroxyl radicals through reacting with H 2 O 2 and consuming glutathione (GSH) of the BME, thereby contributing to more efficient synergistic therapeutic effect. Meanwhile, FePN SAzyme could catalyze biofilm‐overexpressed H 2 O 2 decomposing into O 2 and overcome the hypoxia of biofilm, which significantly enhances the susceptibility of biofilm and increases the synergistic efficacy. Most importantly, the synergistic therapy of bacterial‐induced infection diseases can be switched on by the internal and external stimuli simultaneously, resulting in minimal nonspecific damage to healthy tissue. These remarkable characteristics of FePN SAzyme not only develop an innovative strategy for the BME‐activated combination therapy but also open a new avenue to explore other nanozyme‐involved nanoplatforms for bacterial biofilm infections.