Chemical conjugation of urokinase to magnetic nanoparticles for targeted thrombolysis

Thrombolytic therapy is an important treatment for thrombosis, a life-threatening condition in cardiovascular diseases. However, the traditional thrombolytic therapies have often been associated with the risk of severe bleeding. By conjugating urokinase with magnetic nanoparticles (MNPs), we have presented a strategy to control thrombolysis within a specific site. The covalent bioconjugate of urokinase and dextran-coated MNPs was synthesized and isolated. Thrombolysis by the conjugate was studied under a magnetic field in a rat arteriovenous shunt thrombosis model. The magnetic field was generated by two AlNiCo permanent magnets around the site of thrombus. The magnetic field enhanced the thrombolytic efficacy of the conjugate by 5-fold over urokinase with no reduction in plasma fibrinogen and little prolonged bleeding time. It suggested that thrombolysis had been specifically directed to the desired site by the magnetic carrier under the magnetic field. Additionally, the conjugate had a longer half-life than urokinase in circulation.