ABSTRACT Combining sonodynamic therapy (SDT) with catalytic therapy presents a promising strategy for cancer treatment. However, its development has been constrained by the scarcity of efficient sonosensitizers and limited control over catalytic processes. Herein, a ZnY dual single‐atom nanozyme (DAzyme) anchored on a zeolitic imidazolate framework‐8 (ZIF‐8) substrate is developed to function as both a sonosensitizer and a nanozyme, synergistically promoting reactive oxygen species (ROS) generation and antitumor activity. Density functional theory (DFT) calculations reveal that the synergistic interplay between adjacent Zn─Y diatomic sites endow the ZnY DAzyme with a metalloid‐like electronic structure. This unique electronic configuration significantly facilitates the generation and separation of electron‐hole pairs under ultrasound stimulation, thereby enhancing the SDT performance. In addition to its sonodynamic function, the nanozyme exhibits peroxidase (POD)‐like activity, catalyzing the conversion of endogenous H 2 O 2 into •OH within the tumor microenvironment (TME), contributing to cancer cell destruction. In vitro and in vivo experiments demonstrate that the ZnY DAzyme, under ultrasound stimulation, provides superior tumor suppression compared to single‐metal analogues. Collectively, this work establishes a DAzyme‐based strategy for synergistic SDT and catalytic therapy, showcasing its potential for enhancing cancer therapy.
Jiang et al. (2026) studied this question.