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

作者：Seo Junyoung; Al Hilal Taslim A; Jee Jun Goo; Kim Yong Lim; Kim Ha Jeong; Lee Byung Heon; Kim Soyoun^*; Kim In San^*

来源：Nanomedicine: Nanotechnology, Biology and Medicine , 2018, 14(3): 633-642.

DOI：10.1016/j.nano.2017.12.022

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

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.

• 出版日期2018-4