A dual enzyme-mimicking COF sonosensitizer potentiates cancer sonodynamic therapy via cascade oxygenation and ROS storm
Sonodynamic therapy (SDT) faces critical limitations from inefficient sonosensitizers and the hypoxic tumor microenvironment, which curtail reactive oxygen species (ROS) generation. Here, we report a dual enzyme-mimicking sonosensitizer, termed sonozyme, engineered by integrating platinum nanoparticles (Pt NPs) with a tailored covalent organic framework (Y-COF). The spatially separated donor-acceptor architecture optimizes the band position of Y-COF, conferring intrinsic sonodynamic activity. Pt NPs further enhance ultrasound-triggered ROS generation by promoting exciton separation and transfer. Notably, sonozyme exhibits catalase (CAT) and peroxidase (POD) mimetic activities, converting endogenous H2O2 into O2 and ·OH, thereby alleviating hypoxia and augmenting oxidative stress. In vitro assays demonstrated significantly enhanced ROS production and cancer cell death under ultrasound irradiation. In vivo studies confirmed that sonozyme effectively suppresses tumor progression without observable systemic toxicity. This work presents a paradigm for designing high-performance multifunctional sonosensitizers, offering a promising strategy for cancer therapy.