Microenvironment‐Responsive Injectable Thermosensitive Hydrogel Incorporating Nanozymes for Synergistic Breast Cancer Therapy and Postsurgical Adjuvant Treatment

Abstract Tumor recurrence and wound infection present significant challenges to patient recovery following surgery, underscoring the need for effective therapeutic strategies to improve patient prognosis by mitigating these complications. This study introduces novel synthesis methods for honeycomb‐like CuMnOx nanozymes and CuO₂ nanoflowers with multienzymatic activity and pH‐responsive properties. The enzymatic activities of CuMnOx can be regulated by pH changes in tumor or wound microenvironments, while CuO₂ nanoflowers overcome the limitation of insufficient endogenous H₂O₂ and release ROS in weakly acidic conditions. To realize their synergistic effects, CuMnOx and CuO₂ nanozymes, along with the photothermal agent IR820, are co‐assembled into low‐melting point agarose solution, forming a thermosensitive nanozyme‐based hydrogel (CuMnOx@CuO₂@IR820 hydrogel, CMCI Gel), which facilitates controlled drug delivery and exerts enhanced therapeutic efficiency under low‐temperature photothermal therapy (LTPTT, <48 °C). In vitro and in vivo studies demonstrated that CMCI Gel effectively ablated tumor cells and a range of bacteria, including drug‐resistant bacteria like MRSA. Furthermore, it reduces inflammation, promotes vascular regeneration and collagen deposition, and accelerates wound healing. The injectability and thermosensitivity of the hydrogel allow for localized treatment, minimizing systemic side effects. Overall, these therapeutic benefits highlight CMCI Gel as a promising adjunctive therapy to prevent postsurgery tumor recurrence and wound infection.