Multienzyme-like polyoxometalate for oxygen-independent sonocatalytic enhanced cancer therapy

Artificially synthesized nanozymes exhibit enzymatic activity similar to that of natural enzymes. However, in the complex tumor microenvironment, their diversity and catalytic activity show significant variations, limiting their effectiveness in catalytic therapy. Developing artificial enzymes with multiple enzymatic activities and spatiotemporal controllable catalytic abilities is of great clinical significance. Herein, we propose a novel strategy for synergistic enzyme catalysis and sonocatalytic therapy of tumors using polyoxometalates-based nanozymes. Copper-doped molybdenum-based polyoxometalates (denoted as CP) were rapidly synthesized at room temperature through a one-step method. CP contains mixed-valence states of Cu⁺/Cu²⁺ and Mo⁵⁺/Mo⁶⁺ ions, endowing it with enzyme-like activities of peroxidase, catalase, and glutathione peroxidase. Additionally, the incorporation of copper ions introduces oxygen vacancies into the nano-polyoxometalate, which not only reduces the bandgap but also enhances carrier separation efficiency, thereby improving the sonocatalytic performance of CP as a semiconductor. The combined effects of enzyme-like catalysis and sonocatalysis generate multiple reactive oxygen species (ROS), synergistically depleting glutathione (GSH) and disrupting the redox homeostasis of the tumor, inducing ferroptosis in tumor cells and thereby inhibiting tumor proliferation. This study provides new insights into the design of artificial nanozymes with multiple enzymatic activities and ultrasound activation functions for combined tumor therapy.