• • Sonozyme integrates Pt NPs with Y-COF, achieving dual enzyme-mimicking activities (CAT and POD) that convert H2O2 into O2 and ·OH, alleviating hypoxia and boosting ROS storm; in vivo tumor suppression was significant with no systemic toxicity.
• • The donor-acceptor structural design of Y-COF optimizes band positions, enhancing intrinsic sonodynamic activity; Pt NPs further improve exciton separation and transfer, increasing ultrasound-triggered ROS generation.
• • Sonozyme demonstrates catalase-like and peroxidase-like activities, enabling cascade oxygenation and ROS amplification, which are critical for overcoming TME hypoxia and enhancing SDT efficacy.
• • In vivo experiments show effective tumor growth inhibition under ultrasound irradiation with no observable systemic toxicity, indicating potential for clinical translation.