A targeted ferritin-microplasmin based thrombolytic nanocage selectively dissolves blood clots
- Authors
- Seo, Junyoung; Al-Hilal, Taslim A.; Jee, Jun-Goo; Kim, Yong-Lim; Kim, Ha-Jeong; Lee, Byung-Heon; Kim, Soyoun; Kim, In-San
- Issue Date
- Apr-2018
- Publisher
- ELSEVIER
- Keywords
- Thrombolysis; Nanoparticle; Ferritin; Microplasmin; Clot targeting peptide
- Citation
- NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE, v.14, no.3, pp.633 - 642
- Indexed
- SCIE
SCOPUS
- Journal Title
- NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
- Volume
- 14
- Number
- 3
- Start Page
- 633
- End Page
- 642
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/76656
- DOI
- 10.1016/j.nano.2017.12.022
- ISSN
- 1549-9634
- 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 (mu Pn); CLT recognizes fibrin-fibronectin complexes in clots, mu Pn efficiently dissolves clots, and the assembly of double chambered sFt (CLT-sFt-mu Pn) into nanocage structure protects the activated-mu Pn from its circulating inhibitors. Importantly, activated CLT-sFt-mu Pn thrombolytic nanocage showed a prolonged circulatory life over activated-mu Pn and efficiently lysed the preexisting clots in both arterial and venous thromboses models. Thus, CLT-sFt-mu Pn thrombolytic nanocage platform represents the prototype of a targeted clot-busting agent with high efficacy and safety over existing thrombolytic therapies. (c) 2018 Elsevier Inc. All rights reserved.
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Collections - Graduate School > KU-KIST Graduate School of Converging Science and Technology > 1. Journal Articles
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