A targeted ferritin-microplasmin based thrombolytic nanocage selectively dissolves blood clots

Junyoung Seo, Taslim A. Al-Hilal, Jun Goo Jee, Yong Lim Kim, Ha Jeong Kim, Byung Heon Lee, Soyoun Kim, In-San Kim

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

The use of thrombolytic therapies is limited by an increased risk of systemic hemorrhage due to lysis of hemostatic clots. We sought to develop a plasmin-based thrombolytic nanocage that efficiently dissolves the clot without causing systemic fibrinolysis or disrupting hemostatic clots. Here, we generated a double chambered short-length ferritin (sFt) construct that has an N-terminal region fused to multivalent clot targeting peptides (CLT: CNAGESSKNC) and a C-terminal end fused to a microplasmin (μPn); CLT recognizes fibrin–fibronectin complexes in clots, μPn efficiently dissolves clots, and the assembly of double chambered sFt (CLT-sFt-μPn) into nanocage structure protects the activated-μPn from its circulating inhibitors. Importantly, activated CLT-sFt-μPn thrombolytic nanocage showed a prolonged circulatory life over activated-μPn and efficiently lysed the preexisting clots in both arterial and venous thromboses models. Thus, CLT-sFt-μPn thrombolytic nanocage platform represents the prototype of a targeted clot-busting agent with high efficacy and safety over existing thrombolytic therapies.

Original languageEnglish
Pages (from-to)633-642
Number of pages10
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume14
Issue number3
DOIs
Publication statusPublished - 2018 Apr 1

Keywords

  • Clot targeting peptide
  • Ferritin
  • Microplasmin
  • Nanoparticle
  • Thrombolysis

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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