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Targeted Antithrombotic Protein Micelles
Author(s) -
Kim Wookhyun,
Haller Carolyn,
Dai Erbin,
Wang Xiowei,
Hagemeyer Christoph E.,
Liu David R.,
Peter Karlheinz,
Chaikof Elliot L.
Publication year - 2015
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201408529
Subject(s) - micelle , chemistry , antithrombotic , platelet activation , thrombin , thrombomodulin , biophysics , thrombus , platelet , ligand (biochemistry) , receptor , biochemistry , medicine , immunology , biology , surgery , aqueous solution , cardiology
Activated platelets provide a promising target for imaging inflammatory and thrombotic events along with site‐specific delivery of a variety of therapeutic agents. Multifunctional protein micelles bearing targeting and therapeutic proteins were now obtained by one‐pot transpeptidation using an evolved sortase A. Conjugation to the corona of a single‐chain antibody (scFv), which binds to the ligand‐induced binding site (LIBS) of activated GPIIb/IIIa receptors, enabled the efficient detection of thrombi. The inhibition of thrombus formation was subsequently accomplished by incorporating the catalytically active domain of thrombomodulin (TM) onto the micelle corona for the local generation of activated protein C, which inhibits the formation of thrombin. An effective strategy has been developed for the preparation of protein micelles that can be targeted to sites of activated platelets with broad potential for treatment of acute thrombotic events.