Channel‐trap coupled charge modulation in sulfur‐vacancy‐rich nanotransducer for enhanced dual‐mode cancer catalytic therapy

Defect engineering provides a powerful approach for modulating charge flow and catalytic activity in nanocatalysts, but its application in cancer therapy remains still underexplored. Here, we designed a sulfur vacancy‐rich metal sulfide‐carbon heterojunctions (ZnS–NC x ) that integrates piezoelectric sonodynamic activation with multi‐enzyme‐mimicking catalysis to achieve dual‐modality reactive oxygen species (ROS) generation and amplification. Specifically, sulfur vacancies introduce a channel–trap coupled electron pathway in ZnS–NC x . The vacancies act as electron traps, promoting charge separation under ultrasound‐induced piezoexcitation, while also functioning as atomically dispersed conduction channels that accelerate intra‐lattice electron relay toward catalytic sites. This dual regulation of charge dynamics not only enhances ultrasound‐driven ROS generation but also boosts the intrinsic peroxidase and glutathione oxidase‐like activities of ZnS–NC x . As a result, ROS burst and glutathione (GSH) depletion occur simultaneously in the tumor microenvironment, triggering severe oxidative damage and cell cycle arrest in cancer cells, ultimately leading to their death. Mechanistic analyses reveal that sulfur vacancy engineering optimizes the electronic structure, enhances carrier mobility, and refines electron transport pathways, facilitating efficient charge transfer and endowing the material with superior sonodynamic and enzyme‐mimicking activity. Both in vitro and in vivo evaluations demonstrate that ZnS–NC x induces potent oxidative damage and significantly inhibits tumor growth. This work establishes vacancy‐engineered metal sulfides as next‐generation nanotransducers, where coordinated channel–trap charge pathways enable effective ROS‐mediated cancer therapy.