Cascade Energy Transformation in Hybrid Nanosensitizer Enables Ultrasound-Activated Luminescence Imaging and Enhanced Sonodynamic Therapy.

Optical imaging plays a pivotal role in the diagnosis and management of cancer, yet conventional techniques often suffer from limitations such as tissue autofluorescence, insufficient imaging depth, and signal persistence. Here, we introduce a hybrid nanosensitizer, SPNs(SP1)@CoOOH, that leverages cascade energy transformation (ultrasonic → chemical → photonic energy) to enable ultrasound-activated luminescence imaging concomitant with enhanced sonodynamic therapy (SDT). By integrating semiconducting polymer nanoparticles (SPNs) with cobalt oxide hydroxide (CoOOH), our platform facilitates dual-pathway reactive oxygen species (ROS) generation under acidic and ultrasound costimulation. In this system, the ultrasound enhanced the chemodynamic effect of CoOOH to catalyze water into singlet oxygen, while ultrasound improves electron-hole separation within the SPNs, leading to efficient hydroxyl radical formation. This dual mechanism results in a 3.5-fold increase in ROS production relative to SPNs alone and triggers ROS-thiophene interactions that emit luminescence. Notably, the emitted luminescence correlates linearly with ROS levels and tumor inhibition rates, offering a robust method for a real-time monitoring therapeutic process. Furthermore, our modular design extends to other organic systems, including cyanine and porphyrin-based nanostructures, achieving up to 14.2-fold enhancements in ROS generation and 6.3-fold increases in luminescence intensity. By addressing the dual challenges of inefficient ROS production and real-time monitoring in SDT, our study lays the foundation for next-generation ultrasound-driven theranostics, paving the way for luminescence imaging-guided, personalized cancer therapy.