Abstract: A multifunctional liposomal nanoplatform (OF/UK@cLips) has been engineered for targeted thrombolysis. This was accomplished by encapsulating urokinase (UK) and oleic acid-modified Fe?O? nanoparticles within cRGD-functionalized thermosensitive liposomes. The system leverages magnetic targeting and near-infrared (NIR) light-triggered drug release to enhance thrombolytic efficacy and mitigate systemic side effects. In vitro studies demonstrate controlled UK release upon NIR irradiation, high biocompatibility, minimal hemolysis, and specific targeting of activated platelets through cRGD - integrin binding. Under magnetic and NIR guidance, significant thrombolysis effects are observed, surpassing the efficacy of free UK. In a FeCl3-induced rat carotid thrombosis model, the OF/UK@cLips + NIR + Mag treatment restores blood flow to approximately 380 mm/s within 60 min and reduces the thrombus area to approximately 18%, indicating dual-targeting efficacy and improved drug bioavailability. No significant adverse effects are observed on coagulation, liver function, or inflammation, confirming high biosafety. Collectively, these findings indicate that OF/UK@cLips represents a promising targeted nanotherapy for the safe and effective management of arterial thrombosis.

Keywords: targeted thrombolysis, liposomes, urokinase, cRGD, arterial thrombosis