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

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Abstract

Systemic thrombolysis with intravenous tissue plasminogen activator (tPA) remains the only proven treatment that is effective in improving the clinical outcome of patients with acute ischemic stroke. However, thrombolytic therapy has some major limitations such as hemorrhage, neurotoxicity, and the short time window for the treatment. In this study, we designed iron oxide (Fe3O4) nanorods loaded with 6% tPA, which could be released within ~30 min. The Fe3O4 nanorods could be targeted to blood clots under magnetic guidance. In addition, the release of tPA could be significantly increased using an external rotating magnetic field, which subsequently resulted in a great improvement in the thrombolytic efficiency. Systematic and quantitative studies revealed the fundamental physical processes involved in the enhanced thrombolysis, while the in vitro thrombolysis assay showed that the proposed strategy could improve thrombolysis and recanalization rates and reduce the risk of tPA-mediated hemorrhage in vivo. Such a strategy will be very useful for the treatment of ischemic stroke and other deadly thrombotic diseases such as myocardial infarction and pulmonary embolism in clinical settings.

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Authors and Affiliations

  1. Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China

    Jiangnan Hu, Shengwei Huang, Qichuan ZhuGe & Kunlin Jin

  2. Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas, 76107, USA

    Jiangnan Hu, Shengwei Huang & Kunlin Jin

  3. Department of Physics and Astronomy, Nanoscale Science and Engineering Center, University of Georgia, Athens, Georgia, 30602, USA

    Weijie Huang & Yiping Zhao

Authors
  1. Jiangnan Hu
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  2. Weijie Huang
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  3. Shengwei Huang
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  4. Qichuan ZhuGe
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  5. Kunlin Jin
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  6. Yiping Zhao
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Correspondence to Qichuan ZhuGe, Kunlin Jin or Yiping Zhao.

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These authors contributed equally to this work.

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Hu, J., Huang, W., Huang, S. et al. Magnetically active Fe3O4 nanorods loaded with tissue plasminogen activator for enhanced thrombolysis. Nano Res. 9, 2652–2661 (2016). https://doi.org/10.1007/s12274-016-1152-4

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  • DOI: https://doi.org/10.1007/s12274-016-1152-4

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