Construction of fibrin-targeted nanoparticles for imaging diagnosis and treatment of arterial thrombosis

Abstract

The clinical application of conventional thrombolytic drugs is limited due to the difficulty in precisely targeting the thrombus site and side effects such as severe bleeding. In order to specifically image thrombus for diagnosis and thrombolytic therapy, a CREKA-targeted and pH-responsive drug release nano-delivery system, called LK/PDB/IR820-CREKA NPs, was constructed. In vitro experiments showed that NPs had good pH responsiveness and biocompatibility. The in vitro thrombolytic rate was as high as 46% and the NPs had a strong thrombus-binding ability. In an FeCl₃-induced carotid artery thrombosis mouse model, PDB/IR820-CREKA NPs could specifically target thrombus, which enabled accurate diagnosis of thrombus sites. Targeted nanoparticle-encapsulated lumbrokinase at a dose of 900 U per 10 g significantly reduced the total protein content at the thrombus site, while reducing the risk of non-specific bleeding. Based on the thrombus-specific imaging and therapeutic activity, this nano-delivery system has the potential to be used for the treatment of thrombotic vascular diseases.