title: Targeted antithrombotic protein micelles.
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.
authors.affiliation: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis St, Suite 9F, Boston, MA 02115 (USA); the Wyss Institute of Biologically Inspired Engineering of Harvard University, Boston, MA (USA).
authors.forename: Wookhyun
authors.initials: W
authors.lastname: Kim
authors.forename: Carolyn
authors.initials: C
authors.lastname: Haller
authors.forename: Erbin
authors.initials: E
authors.lastname: Dai
authors.forename: Xiowei
authors.initials: X
authors.lastname: Wang
authors.forename: Christoph E
authors.initials: CE
authors.lastname: Hagemeyer
authors.forename: David R
authors.initials: DR
authors.lastname: Liu
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Peter
authors.forename: Elliot L
authors.initials: EL
authors.lastname: Chaikof
mesh_terms: D019881:Aminoacyltransferases / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D008823:Micelles; D010455:Peptides / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use; D015539:Platelet Activation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry / Q000378:metabolism; D057127:Single-Chain Antibodies / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000378:metabolism; D018180:Thrombomodulin / Q000737:chemistry / Q000378:metabolism; D013927:Thrombosis / Q000188:drug therapy / Q000276:immunology
chemical_list: D001426:Bacterial Proteins; D005343:Fibrinolytic Agents; D008823:Micelles; D010455:Peptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D057127:Single-Chain Antibodies; D018180:Thrombomodulin; D019881:Aminoacyltransferases; C120542:sortase A; D013917:Thrombin; D003546:Cysteine Endopeptidases
keywords: bioconjugation; drug delivery; micelles; therapeutic proteins; thrombosis