Ultrasound-driven atherosclerosis nanomedicine: from mechanical, cavitation, and sonodynamic therapies to bedside translation

Atherosclerosis (AS) is a leading cause of cardiovascular mortality worldwide, highlighting an urgent need for innovative, non-invasive therapies to address plaque instability and acute cardiovascular events. Ultrasound technology has emerged as a transformative platform, utilizing mechanical, cavitation, and sonodynamic effects to specifically target the pathological mechanisms of AS. This review systematically explores three key therapeutic strategies: first, ultrasound thermal and mechanical effects for direct plaque disruption and enhanced drug delivery; second, cavitation-mediated thrombolysis and modulation of the plaque microenvironment, and third, sonodynamic effects triggering reactive oxygen species (ROS)-induced apoptosis or autophagy. Furthermore, this review provides a comprehensive summary of the clinical progress of ultrasound-driven thrombolytic therapy and sonodynamic therapy for AS. Although ultrasound therapy for AS has achieved preclinical success with some advancing to clinical trials, challenges remain in balancing ultrasound parameters, reducing ROS toxicity, and ensuring the long-term biosafety of sonosensitizers. By discussing ultrasound therapeutic mechanisms, sonosensitizer design, and clinical applications, this review aims to provide valuable insights for the advancement of the nanomedicine field.