Urokinase-Gold Nanoparticle Conjugates as Theranostic Agents for Thrombotic Diseases

Abstract

The thrombotic disease is one of the leading cause of death worldwide. Although thrombolytic drugs such as various plasminogen activators have been used to dissolve a thrombus, their use has been limited by their short half-life and hemorrhage side effects. There have been several studies to combine nanoparticle with plasminogen activators, but there has not been combination with the CT imaging agents. Because CT imaging is suitable for imaging of the thrombus with a fast scan time, the combination of the thrombolytic agents and the CT imaging agents will provide efficient treatment. In this study, we developed theranostic agents combining gold nanoparticles for CT imaging and urokinase for therapeutic effect. The formation and surface modification of nanoparticles were confirmed by measurement of TEM, DLS, UV, and FT-IR. Urokinase and GC-AuNP combined UK-GC-AuNPs had a core size of 20 nm and a hydrodynamic diameter of about 190 nm. In vitro release test, it was confirmed that urokinase was well attached to UK-GC-AuNPs. In vitro thrombolysis test, UK-GC-AuNPs dissolved the thrombus within 30 minutes. In vivo thrombolysis test, UK-GC-AuNPs were caught in the mesh structure of thrombus and directly imaged the thrombus. After UK-GC-AuNPs were caught in the thrombus, UK on GC-AuNPs continuously dissolved the thrombus and after 48 hours, almost completely dissolve the thrombus. Consequently, we synthesized a theranostic agent by combination of urokinase and gold nanoparticles, and confirmed its imaging ability and thrombolysis effect in vitro and in vivo. This research will provide platform for combined CT imaging and therapy of thrombotic diseases.