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.
|Number of pages||10|
|Journal||Nanomedicine: Nanotechnology, Biology, and Medicine|
|Publication status||Published - 2018 Apr|
Bibliographical noteFunding Information:
Funding: This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2015R1D1A3A01019018); the National Research Foundation of Korea (NRF) grant funded by the Korea government (2014R1A5A2009242); the National Research Foundation of Korea (NRF) funded by the Korea government (2017R1A3B1023418).
- Clot targeting peptide
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Molecular Medicine
- Biomedical Engineering
- Materials Science(all)
- Pharmaceutical Science