Number of the records: 1
Targeting Human Thrombus by Liposomes Modified with Anti-Fibrin Protein Binders
- 1.
SYSNO ASEP 0521340 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Targeting Human Thrombus by Liposomes Modified with Anti-Fibrin Protein Binders Author(s) Petroková, Hana (BTO-N) RID
Mašek, J. (CZ)
Kuchař, Milan (BTO-N) RID
Wunschova, A. V. (CZ)
Štikarová, J. (CZ)
Bartheldyová, E. (CZ)
Kulich, P. (CZ)
Hubatka, F. (CZ)
Kotouček, J. (CZ)
Knötigová, P.T. (CZ)
Vohlidalova, E. (CZ)
Hezova, R. (CZ)
Mašková, E. (CZ)
Macaulay, S. (CZ)
Dyr, J. E. (CZ)
Raška, M. (CZ)
Mikulik, R. (CZ)
Malý, Petr (BTO-N) RID, ORCID
Turánek, J. (CZ)Number of authors 19 Article number 642 Source Title Pharmaceutics. - : MDPI
Roč. 11, č. 12 (2019)Number of pages 21 s. Language eng - English Country CH - Switzerland Keywords fibrin ; thrombus imaging ; binding protein ; thrombus targeting Subject RIV FR - Pharmacology ; Medidal Chemistry OECD category Pharmacology and pharmacy R&D Projects NV16-30299A GA MZd - Ministry of Health (MZ) ED1.1.00/02.0109 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support BTO-N - RVO:86652036 UT WOS 000506874300046 DOI 10.3390/pharmaceutics11120642 Annotation Development of tools for direct thrombus imaging represents a key step for diagnosis and treatment of stroke. Nanoliposomal carriers of contrast agents and thrombolytics can be functionalized to target blood thrombi by small protein binders with selectivity for fibrin domains uniquely formed on insoluble fibrin. We employed a highly complex combinatorial library derived from scaffold of 46 amino acid albumin-binding domain (ABD) of streptococcal protein G, and ribosome display, to identify variants recognizing fibrin cloth in human thrombus. We constructed a recombinant target as a stretch of three identical fibrin fragments of 16 amino acid peptide of the B beta chain fused to TolA protein. Ribosome display selection followed by large-scale Enzyme-Linked ImmunoSorbent Assay (ELISA) screening provided four protein variants preferentially binding to insoluble form of human fibrin. The most specific binder variant D7 was further modified by C-terminal FLAG/His-Tag or double His-tag for the attachment onto the surface of nanoliposomes via metallochelating bond. D7-His-nanoliposomes were tested using in vitro flow model of coronary artery and their binding to fibrin fibers was demonstrated by confocal and electron microscopy. Thus, we present here the concept of fibrin-targeted binders as a platform for functionalization of nanoliposomes in the development of advanced imaging tools and future theranostics. Workplace Institute of Biotechnology Contact Monika Kopřivová, Monika.Koprivova@ibt.cas.cz, Tel.: 325 873 700 Year of Publishing 2020 Electronic address https://www.mdpi.com/1999-4923/11/12/642
Number of the records: 1