Bioconjugation of recombinant tissue plasminogen activator to magnetic nanocarriers for targeted thrombolysis

Hung Wei Yang, Mu Yi Hua, Kun Ju Lin, Shiaw Pyng Wey, Rung Ywan Tsai, Siao Yun Wu, Yi Ching Lu, Hao Li Liu, Tony Wu, Yunn Hwa Ma*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

57 Scopus citations

Abstract

Low-toxicity magnetic nanocarriers (MNCs) composed of a shell of poly [ aniline-co-N-(1-one-butyric acid) aniline] over a Fe3O4 magnetic nanoparticle core were developed to carry recombinant tissue plasminogen activator (rtPA) in MNC-rtPA for targeted thrombolysis. With an average diameter of 14.8 nm, the MNCs exerted superparamagnetic properties. Up to 276 μg of active rtPA was immobilized per mg of MNCs, and the stability of the immobilized rtPA was greatly improved during storage at 4°C and 25°C. In vitro thrombolysis testing with a tubing system demonstrated that magnet-guided MNC-rtPA showed significantly improved thrombolysis compared with free rtPA and reduced the clot lysis time from 39.2 ± 3.2 minutes to 10.8 ± 4.2 minutes. In addition, magnet-guided MNC-rtPA at 20% of the regular rtPA dose restored blood flow within 15-25 minutes of treatment in a rat embolism model without triggering hematological toxicity. In conclusion, this improved system is based on magnetic targeting accelerated thrombolysis and is potentially amenable to therapeutic applications in thromboembolic diseases.

Original languageEnglish
Pages (from-to)5159-5173
Number of pages15
JournalInternational Journal of Nanomedicine
Volume7
DOIs
StatePublished - 2012

Keywords

  • Magnetic nanocarriers
  • Magnetic targeting
  • Recombinant tissue plasminogen activator
  • Targeting therapy
  • Thrombolysis

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