Improving Ischemic Stroke Treatment with Functional Magnetic Nanomotor

The treatment of ischemic stroke remains a daunting task as few therapeutic strategies have proven to be effective. Systemic thrombolysis with intravenous tissue plasminogen activator (tPA) remains the only proven treatment to improve clinical outcome of patients with acute ischemic stroke. But because of an increased risk of hemorrhage beyond 4.5 hours after onset of stroke, only certain stroke patients (1-2%) can benefit from tPA treatment. Current limitations of intravascular thrombolysis are primarily due to the inefficient/ineffective penetration of the systemically circulating tPA into the thrombus core. To improve tPA-induced thrombolysis and recanalization rates, we have developed a new strategy by incorporating rotary magnetic iron oxide (Fe₃O₄)-nanorods powered by an external magnetic field with the tPA delivery. Once the nanorods encounter the blood clot in the artery, it could not only improve the mass transport of the tPA-clot reaction, but also could mechanically disrupt the clot network to make a larger opening in the clot. Additionally, when magnetic nanorods are covalently bound to tPA with retained enzyme activity, the tPA functionalized magnetic nanorods can target to the blood clot in vivo under the guidance of an external magnet and tPA can subsequently be efficiently delivered at the site of embolism at high concentration to facilitate thrombolysis. Thus, an efficient tPA delivery system to the brain in combination with magnetic nanorods overcomes the limitations of current therapy with tPA alone. In a mouse model, we show that with two orders of less concentration of tPA on tPA-magnetic nanorod injection, it takes less than 1/3 time to lyse the blood clot, compared to that of tPA injection alone. In this talk, I will discuss the synthesis, functionalization of the magnetic nanorods, the physical and chemical mechanism of the improved thrombolysis, and the results from both the in vitro and animal tests as well as future challenges