Targeted Antithrombotic Protein Micelles |
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| Authors: | Dr Wookhyun Kim Dr Carolyn Haller Dr Erbin Dai Xiowei Wang Dr Christoph E Hagemeyer Prof David R Liu Prof Karlheinz Peter Prof Elliot L Chaikof |
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| Institution: | 1. Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis St, Suite 9F, Boston, MA 02115 (USA);2. the Wyss Institute of Biologically Inspired Engineering of Harvard University, Boston, MA (USA);3. Atherothrombosis and Vascular Biology, Baker IDI Heart and Diabetes Institute, PO Box 6492, St Kilda Rd Central, Victoria 8008 (Australia);4. Howard Hughes Medical Institute, Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138 (USA) |
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| Abstract: | 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. |
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| Keywords: | bioconjugation drug delivery micelles therapeutic proteins thrombosis |
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