Research Article


2016, 9(9): 2652–2661


Magnetically active Fe3O4 nanorods loaded with tissue plasminogen activator for enhanced thrombolysis

Jiangnan Hu1,2,§, Weijie Huang3,§, Shengwei Huang1,2,§, Qichuan ZhuGe1 (*), Kunlin Jin 1,2 (*), and Yiping Zhao3 (*)

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1 Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
2 Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas 76107, USA
3 Department of Physics and Astronomy, Nanoscale Science and Engineering Center, University of Georgia, Athens, Georgia 30602, USA
§ These authors contributed equally to this work.

Keywords: magnetic nanorods,drug delivery,enhanced thrombolysis,tissue plasminogenactivator,iron oxide
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  • Abstract
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Systemic thrombolysis with intravenous tissue plasminogen activator (tPA)remains the only proven treatment that is effective in improving the clinicaloutcome of patients with acute ischemic stroke. However, thrombolytic therapyhas some major limitations such as hemorrhage, neurotoxicity, and the shorttime window for the treatment. In this study, we designed iron oxide (Fe3O4)nanorods loaded with 6% tPA, which could be released within ~30 min. TheFe3O4 nanorods could be targeted to blood clots under magnetic guidance. Inaddition, the release of tPA could be significantly increased using an externalrotating magnetic field, which subsequently resulted in a great improvementin the thrombolytic efficiency. Systematic and quantitative studies revealed thefundamental physical processes involved in the enhanced thrombolysis, whilethe in vitro thrombolysis assay showed that the proposed strategy could improvethrombolysis and recanalization rates and reduce the risk of tPA-mediatedhemorrhage in vivo. Such a strategy will be very useful for the treatment ofischemic stroke and other deadly thrombotic diseases such as myocardial infarctionand pulmonary embolism in clinical settings.
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Magnetically active Fe3O4 nanorods loaded with tissue plasminogen activator for enhanced thrombolysis. Nano Res. 2016, 9(9): 2652–2661

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