Ultrasound-Mediated Thrombolysis: From Mechanistic Insights to Advanced Nanoplatforms and Clinical Translation

Although pharmacological thrombolysis and mechanical thrombectomy are standard treatments for thromboembolic diseases, they are limited by hemorrhagic risks and incomplete revascularization. Ultrasound-mediated thrombolysis (UMT) has emerged as a promising targeted therapy that leverages acoustic cavitation and microstreaming to overcome these limitations. This review elucidates the core biophysical mechanisms of UMT, highlighting how acoustic forces synergize with fibrinolytic agents to enhance drug penetration and disrupt clot architecture. We categorize current technologies ranging from Food and Drug Administration (FDA)-approved catheter-directed systems (e.g., EkoSonic system) to emerging non-invasive histotripsy and stimuli-responsive nanoplatforms, with an emphasis on recent advances in materials-enabled ultrasound therapies. Furthermore, the integration of multimodal imaging and artificial intelligence is discussed as a pathway toward precision closed-loop therapy. By identifying key translational barriers-including challenges in nanoplatform design, cavitation control, and biosafety-this review proposes a paradigm shift from acute recanalization to integrated thrombo-inflammatory management.