TPA Immobilization on Iron Oxide Nanocubes and Localized Magnetic Hyperthermia Accelerate Blood Clot Lysis

Eszter Voros, Minjung Cho, Maricela Ramirez, Anna Lisa Palange, Enrica De Rosa, Jaehong Key, Zsolt Garami, Alan B. Lumsden, Paolo Decuzzi

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The low specificity and high risk of intracranial hemorrhage associated with currently approved thrombolytic therapies limit their efficacy in recanalizing occluded vessels. Here, a nanoscale thrombolytic agent is demonstrated by immobilizing tissue plasminogen activator molecules (tPA) over 20 nm clustered iron oxide nanocubes (NCs). The resulting nanoconstructs (tPA-NCs) are capable of dissolving clots via both direct interaction of tPA with the fibrin network (chemical lysis) and localized hyperthermia upon stimulation of superparamagnetic NCs with alternating magnetic fields (AMFs) (mechanical lysis). In vitro, as compared to free tPA, the proposed nanoconstructs demonstrate a ≈100-fold increase in dissolution rate, possibly because of a more intimate interaction of tPA with the fibrin network. The clot dissolution rate is further enhanced (≈10-fold) by mild, localized heating resulting from the exposure of tPA-NCs to AMF. Intravital microscopy experiments demonstrate blood vessel reperfusion within a few minutes post tail vein injection of tPA-NCs. The proposed nanoconstructs also exhibit high transverse relaxivity (>400 × 10-3 m-1 s-1) for magnetic resonance imaging. The multifunctional properties and the 3 orders of magnitude enhancement in clot dissolution make tPA-NCs a promising nano-theranosis agent in thrombotic disease.

Original languageEnglish
Pages (from-to)1709-1718
Number of pages10
JournalAdvanced Functional Materials
Volume25
Issue number11
DOIs
Publication statusPublished - 2015 Jan 21

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics

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    Voros, E., Cho, M., Ramirez, M., Palange, A. L., De Rosa, E., Key, J., Garami, Z., Lumsden, A. B., & Decuzzi, P. (2015). TPA Immobilization on Iron Oxide Nanocubes and Localized Magnetic Hyperthermia Accelerate Blood Clot Lysis. Advanced Functional Materials, 25(11), 1709-1718. https://doi.org/10.1002/adfm.201404354