Defect-engineered sonopiezoelectric nanosheets enable sacrificial-agent-free hydrogen peroxide self-cycling for enhanced pancatalytic therapy

High concentrations of hydrogen peroxide (H 2 O 2 ) can impair tumor cell death by forming reactive species, such as hydroxyl radicals (·OH), or by releasing oxygen, which enhances the production of 1 O 2 and·O 2 − in dynamic therapies. Limited H 2 O 2 availability hinders effective reactive oxygen species generation in sonocatalytic therapy. To overcome this challenge, sulfur-defective ZnIn 2 S 4 nanosheets were engineered as sonopiezoelectric sensitizers, enabling sacrificial-agent-free H 2 O 2 production and pancatalytic tumor therapy. These nanosheets demonstrated a distinctive H 2 O 2 self-supplying and self-consumption capability, allowing in situ H 2 O 2 generation within the tumor microenvironment and its subsequent consumption via peroxidase- and catalase-mimicking activities. The first-principle simulations revealed that H 2 O 2 production occurs via 2-electron oxygen reduction and water oxidation. RNA sequencing (RNA-seq) and western blot analyses demonstrated that ZnIn 2 S 4 nanosheets induce PANoptosis by modulating key apoptotic proteins. This work provides a representative paradigm of biomaterial design for efficient pancatalytic tumor therapy, laying the foundation for more effective synergistic tumor therapies.