An Asynchronous-Regulated Nanosheet Cascade Amplifies Sonodynamic-Triggered Self-Enhanced DNA Damage for Intensive Tumor Immunotherapy

released from ECHO, respectively, which in turn disrupted ROS clearance for reversing tumor resistance to DNA damage and boosting innate immunity. Simultaneously, Niclosamide inhibited STAT3 in DNA repair response and counteracted immunosuppressive effects. The asynchronous regulation of STING and STAT3 increased ROS absolute content and restrained DNA repairing, facilitating self-enhanced DNA damage, thus intensifying tumor immunotherapy. ECHO effectively targeted tumors with minimal adverse effects, leading to 87% tumor regression and 40% contralateral bilateral tumor elimination. Overall, our asynchronous regulation strategy achieved self-enhancing DNA damage and offered a promising prototype for intensive tumor immunotherapy.