Micro CT imaging assessment for spatial distribution of magnetic nanoparticles in an ex vivo thrombolysis model

In recent nanotechnology development, iron-based magnetic nanoparticles (MNPs) have been used in several investigations on biomedical research for small animal experiments. Their important applications include targeted drug delivery for therapeutic purpose, contrast agent for magnetic resonance imaging, and hyperthermia treatment for tumors. These MNPs can be guided by an external magnetic field due to their physical characteristics of superparamagnetism. In a recent report, authors indicated that covalently bound recombinant tissue plasminogen activator (rtPA) to MNP (MNP-rtPA) with preserved enzyme activity may be guided by a bar magnet and induce target thrombolysis in an embolic model in rats. Delivery of rtPA by binding the thrombolytic drug to MNPs will improve the possibility of the drug to be delivered under magnetic guidance and retained in a local targeted area in the circulation system. In this work, an ex vivo intravascular thrombolysis model was developed to study the impact of external magnetic field on the penetration of MNP-rtPA in the blood clot samples. The samples were then scanned by a micro CT system for quantification. Images of MNPs show strong contrast with their surrounding blood clot materials. The optimum drug loading was found when 0.5 mg/ml rtPA is conjugated with 10 mg SiO2-MNP where 98% drug was attached to the carrier with full retention of its thrombolytic activity. Effective thrombolysis with tPA bound to SiO2-MNP under magnetic guidance was demonstrated in our ex vivo model where substantial reduction in time for blood clot lysis was observed compared with control groups without magnetic field application.