Ultrasound-Induced Cavitation of Immunoliposomes for Rapid Drug Release, Deep Thrombus Penetration, and Enhanced Thrombolysis.

Thrombotic diseases such as ischemic stroke, myocardial infarction, and pulmonary thromboembolism pose significant health risks worldwide. Thrombolytic agents such as urokinase are commonly used to dissolve clots, but their systemic administration can cause bleeding complications due to rapid clearance and a lack of target specificity. We developed a novel drug delivery system using ultrasound-responsive liposomes decorated with PEGylated cyclic RGD peptides. This system was designed to enhance the targeted delivery of urokinase to thrombi to improve the thrombolytic efficacy while minimizing side effects. Ammonium bicarbonate, encapsulated in the liposomes, generated microbubbles under ultrasound exposure that enabled controlled drug release and improved clot disruption through cavitation. The release mechanism of ammonium bicarbonate-induced drug release was investigated using multiple kinetic fitting models. The targeting capability of the liposomes, mediated by the cRGD unit, was demonstrated by flow cytometry and fluorescence microscopy, and supported by molecular docking simulations. Hemolytic and cytotoxicity profiles were evaluated using mouse red blood cells and Human Umbilical Vein Endothelial Cells. Studies using an