水蛭素
凝结
凝血酶
抗凝剂
血栓
肝素
药理学
医学
化学
免疫学
内科学
血小板
作者
Xiao Xu,Xuechao Huang,Ying Zhang,Shi‐Hsiang Shen,Zhizi Feng,He Dong,Can Zhang,Ran Mo
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2020-10-09
卷期号:6 (41)
被引量:30
标识
DOI:10.1126/sciadv.abc0382
摘要
Pathological coagulation, a disorder of blood clotting regulation, induces a number of cardiovascular diseases. A safe and efficient system for the delivery of anticoagulants to mimic the physiological negative feedback mechanism by responding to the coagulation signal changes holds the promise and potential for anticoagulant therapy. Here, we exploit a "closed-loop" controlled release strategy for the delivery of recombinant hirudin, an anticoagulant agent that uses a self-regulated nanoscale polymeric gel. The cross-linked nanogel network increases the stability and bioavailability of hirudin and reduces its clearance in vivo. Equipped with the clot-targeted ligand, the engineered nanogels promote the accumulation of hirudin in the fibrous clots and adaptively release the encapsulated hirudin upon the thrombin variation during the pathological proceeding of thrombus for potentiating anticoagulant activity and alleviating adverse effects. We show that this formulation efficiently prevents and inhibits the clot formation on the mouse models of pulmonary embolism and thrombosis.
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