Intravascular Ultrasound-Guided Local Theranostics Enables Precise Treatment of Atherosclerotic Plaques.

Abstract

Although sonodynamic therapy (SDT) has shown promise in reducing atherosclerotic plaque burden, its clinical application remains confined to superficial lesions, as deep-seated plaques such as those in coronary arteries lack precise imaging guidance and lesion-specific energy delivery. Here, we report an intravascular ultrasound (IVUS)-guided SDT strategy that integrates high-resolution imaging and precise treatment within a single catheter system. Osteopontin (OPN)-targeted bismuth-based nanoparticles (BSNPs), endowed with piezoelectricity through defect-induced symmetry breaking, selectively accumulate in foam cells. Pulsed ultrasound emitted by the IVUS catheter triggers BSNPs to generate reactive oxygen species (ROS) through the modulation of pulse-repetition time (PRT) and pulse width (PW), thereby inducing foam cell apoptosis and promoting plaque regression. With IVUS guidance, the SDT process can be visualized in real time, ensuring precise lesion-specific treatment. Systematic in vitro and in vivo studies demonstrate the effective antiatherosclerotic effect with minimal adverse effects. This imaging-integrated piezo-sonodynamic platform establishes a multifunctional catheter-based ultrasound theranostic strategy, providing a precise and clinically translatable approach for treating atherosclerosis.