RT Journal Article
SR Electronic
T1 Self-regulated hirudin delivery for anticoagulant therapy
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eabc0382
DO 10.1126/sciadv.abc0382
VO 6
IS 41
A1 Xu, Xiao
A1 Huang, Xuechao
A1 Zhang, Ying
A1 Shen, Shiyang
A1 Feng, Zhizi
A1 Dong, He
A1 Zhang, Can
A1 Mo, Ran
YR 2020
UL http://advances.sciencemag.org/content/6/41/eabc0382.abstract
AB 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.