Immuno-modulatory nanozyme film with self-switchable activity for adaptive infection-inflammation-repair cascade in wound infection therapy and healing.

Abstract

The key for nanozymes to achieving sequential infection-inflammation-repair in wound infection therapy and healing lies in how to resolve the contradiction of reactive oxygen species (ROS) regulation between antibacterial therapy and anti-inflammation. Herein, a freestanding pristine CuGeO₃ (CGO) nanozyme film (NF) composed of nanowires is first designed and simply synthesized. Such a NF with flexibility, wet tissue adhesion properties, alongside water/blood absorbing capability could serve as a wound dressing and present superb antibacterial/antibiofilm efficacy for photothermal/chemodynamic synergistic therapy of wound infection owing to its extraordinarily outstanding photothermal performance, and glutathione depletion-enhanced peroxidase-like activity to generate ROS in acidic infection microenvironments (IMEs). Attractively, it is disclosed that after completing infection therapy, the enzyme activity of this CGO NF automatically and continuously switches into catalase-like activity to eliminate ROS as IMEs switches into neutral microenvironments. This promotes the M2 phenotype polarization of macrophages to relieve inflammation and accelerate wound repair. Furthermore, the longer and entangled nanowire structure of the CGO NF prone to retention in the wound site minimizes its toxicity to healthy tissues. Overall, it is the first paradigm to leverage a photothermal NF consisting of inorganic nanomaterials only as a wound dressing. Based on such a safe, effective, activity-switchable NF dressing, adaptive infection-inflammation-repair cascade in wound infection therapy and healing has been realized, achieving 98.7% wound closure within 10 days. We believe this work will foster the therapeutic application of activity-switchable nanozymes, and provide meaningful insights into nanozymes-based wound infection therapy and healing.