A Sprayable Nanoplatform Breaks the Vicious Cycle of Diabetic Wounds via Photoactivated Antioxidant and Drug Delivery

ABSTRACT Diabetic wound healing is still a challenge, because the pathological microenvironment is characterized by a vicious cycle of oxidative stress, hypoxia, infection and chronic inflammation. Herein, we report a near‐infrared (NIR) light‐activated cascade nanodressing incorporated into a sprayable hyaluronic acid hydrogel. Under NIR irradiation, MXene serves not only as a photothermal substrate but also generates an interfacial electronic effect that drastically enhances the multienzyme‐mimicking activities of zinc hexacyanoferrate (ZnHCF), enabling efficient ROS clearance and alleviation of hypoxia. The mild photothermal effect further triggers‐controlled release of deferoxamine (DFO), which cooperates with ZnHCF to chelate free iron ions, thereby suppressing ROS generation at the source. The system also exhibits synergistic photothermal‐nanoknife‐Zn 2+ antibacterial efficacy, promoting macrophage repolarization from an M1 to an M2 phenotype. Moreover, DFO‐induced HIF‐1α upregulation facilitates angiogenesis and collagen deposition. Both in vitro and in vivo studies have confirmed that this sprayable nanodressing with “3A” (anti‐inflammatory, antibacterial, and angiogenic) effect can significantly accelerate the healing of diabetic wounds by improving the chronic wound microenvironment, achieving complete re‐epithelization within 13 days. This work sets the stage for a new generation of on‐demand, activated, synergistic systems, offering a viable path toward treating refractory tissue injuries.