An Immunomodulatory Biomimetic Single-Atomic Nanozyme for Biofilm Wound Healing Management

Nanozyme-driven catalytic antibacterial therapy has become a promising modality for bacterial biofilm infections. However, current catalytic therapy of biofilm wounds is severely limited by insufficient catalytic efficiency, excessive inflammation, and deep tissue infection. Drawing from the homing mechanism of natural macrophages, herein, a hollow mesoporous biomimetic single-atomic nanozyme (SAN) is fabricated to actively target inflamed parts, suppress inflammatory factors, and eliminate deeply organized bacteria for enhance biofilm eradication. In the formulation, this biomimetic nanozyme (Co@SAHSs@IL-4@RCM) consists of IL-4-loaded cobalt SANs-embedded hollow sphere encapsulate by RAW 264.7 cell membrane (RCM). Upon accumulation at the infected sites through the specific receptors of RCM, Co@SAHS catalyze the conversion of hydrogen peroxide into hydroxyl radicals and are further amplify by NIR-II photothermal effect and glutathione depletion to permeate and destroy biofilm structure. This behavior subsequently causes the dissociation of RCM shell and the ensuing release of IL-4 that can reprogram macrophages, enabling suppression of oxidative injury and tissue inflammation. The work paves the way to engineer alternative "all-in-one" SANs with an immunomodulatory ability and offers novel insights into the design of bioinspired materials.