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

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 H2O2 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 H2O2 and consuming glutathione (GSH) of the BME, thereby contributing to more efficient synergistic therapeutic effect. Meanwhile, FePN SAzyme could catalyze biofilm-overexpressed H2O2 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.

Automated summary

A novel FePN SAzyme is introduced in this study for photothermal/chemodynamic synergistic therapy of bacterial-infected wounds in the biofilm microenvironment. The nanozyme shows high efficiency, specificity, and sensitivity, and can be activated by internal and external stimuli in the biofilm, minimizing side effects on healthy tissue.