Organic–Inorganic Hybrid Heterojunction Sonosensitizers for Enhanced Ultrasound-Induced Luminescence Imaging and Sonodynamic Therapy

Ultrasound-induced luminescence offers a light-free imaging modality with deep tissue penetration and spatiotemporal controllability; however, its broader application is hindered by weak luminescent signals that limit imaging depth and signal-to-noise ratios. Here, we report an organic–inorganic heterojunction sonosensitizer, TA@TiO 2, formed by coupling a trianthracene derivative (TA) with titanium oxide (TiO 2 ). Under ultrasound irradiation, the nanoscale charge-transfer interface promotes interfacial charge transfer, significantly enhancing reactive oxygen species (ROS) generation. This increased ROS triggers amplified chemical energy conversion, resulting in a markedly enhanced ultrasound-induced luminescence signal for deep-tissue optical imaging. Compared to TA nanoparticles, TA@TiO 2 exhibits superior signal transmission in scattering media and maintains high luminescence at lower power densities. In vivo studies demonstrate that TA@TiO 2 enables high-contrast imaging of deep-seated tumors, such as pancreatic cancer and glioma, while providing enhanced sonodynamic therapy efficacy. The positive correlation between ultrasound-induced luminescence intensity and ROS generation allows for dynamic, imaging-guided tumor therapy. These results establish heterojunction engineering as a potent strategy for advancing ultrasound-activated theranostics.