Seo, Junyoung Al-Hilal, Taslim A. Jee, Jun-Goo Kim, Yong-Lim Kim, Ha-Jeong Lee, Byung-Heon Kim, Soyoun Kim, In-San 2024-01-19T23:03:19Z 2024-01-19T23:03:19Z 2021-09-03 2018-04 1549-9634 https://pubs.kist.re.kr/handle/201004/121564 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. English ELSEVIER TISSUE-PLASMINOGEN ACTIVATOR ACUTE ISCHEMIC-STROKE PLATFORM NANOPARTICLES MECHANISMS THROMBOSIS PEPTIDES DELIVERY HEPARIN ACID A targeted ferritin-microplasmin based thrombolytic nanocage selectively dissolves blood clots Article 10.1016/j.nano.2017.12.022 1 NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE, v.14, no.3, pp.633 - 642 NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE 14 3 633 642 scie scopus 000429528900001 2-s2.0-85042187067 Nanoscience & Nanotechnology Medicine, Research & Experimental Science & Technology - Other Topics Research & Experimental Medicine Article TISSUE-PLASMINOGEN ACTIVATOR ACUTE ISCHEMIC-STROKE PLATFORM NANOPARTICLES MECHANISMS THROMBOSIS PEPTIDES DELIVERY HEPARIN ACID Thrombolysis Nanoparticle Ferritin Microplasmin Clot targeting peptide