Low‐Intensity Focused Ultrasound‐Responsive Nanobubbles Enhance Thrombus Targeting and Penetration for Highly Effective Thrombolytic Therapy

Owing to the short half‐life, restricted targeting capability, and high bleeding risk associated with thrombolytic drugs, safe and effective thrombolytic therapy remains challenging. Based on the natural targeting and immune escape functions of platelets during thrombosis, spatiotemporally controlled nanobubbles (PAF@M) are developed to specifically target thrombus sites. These nanobubbles are designed by loading an air core of perfluoropentane (PFP) and l ‐arginine within a poly(lactic ‐co ‐glycolic acid) shell and coating it with a platelet membrane. Under stimulation with low‐intensity focused ultrasound (LIFU), physical shear stress promotes deep penetration of the nanobubbles into the thrombus. Moreover, the liquid–gas phase transition of PFP and the release of nitric oxide synergistically enhance ultrasonic cavitation to disrupt the thrombus structure. In terms of mechanism, these gas molecules induce acoustic pore action to disrupt the fibrin network structure, loosening the interior of the thrombus, and act specifically on the surfaces of red blood cells and activated platelets, launching a comprehensive attack on the thrombus. It is believed that PAF@M nanobubbles will delay the progression of thrombosis and achieve safe and highly effective thrombolytic therapy. This simple LIFU response principle has the potential to be a safer and more effective alternative to current pharmaceutical approaches.