Bitistatin-functionalized fluorescent nanodiamond particles specifically bind to purified human platelet integrin receptor αIIbβ3 and activated platelets

Bitistatin-functionalized fluorescent nanodiamond particles specifically bind to purified human platelet integrin receptor αIIbβ3 and activated platelets

Cezary Marcinkiewicz,1,2 Jonathan A Gerstenhaber,1 Mark Sternberg,2 Peter I Lelkes,1 Giora Feuerstein1,2 1Department of Bioengineering, College of Engineering, Temple University, Philadelphia, 2Debina Diagnostic, Inc., Newton Square, PA, USA Abstract: Thromboembolic events (TEE) underwrite key cau...

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Autores principales: Marcinkiewicz C, Gerstenhaber JA, Sternberg M, Lelkes PI, Feuerstein G
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2017
Materias:
carbon nanoparticles
nanodiamond particles
blood clots
imaging
platelet fibrinogen receptor
fluorescence
disintegrin.
Medicine (General)
R5-920
Acceso en línea:https://doaj.org/article/83b9862dbe8d4227bed0ed76381d525c
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spelling oai:doaj.org-article:83b9862dbe8d4227bed0ed76381d525c2021-12-02T01:49:55ZBitistatin-functionalized fluorescent nanodiamond particles specifically bind to purified human platelet integrin receptor αIIbβ3 and activated platelets1178-2013https://doaj.org/article/83b9862dbe8d4227bed0ed76381d525c2017-05-01T00:00:00Zhttps://www.dovepress.com/bitistatin-functionalized-fluorescent-nanodiamond-particles-specifical-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Cezary Marcinkiewicz,1,2 Jonathan A Gerstenhaber,1 Mark Sternberg,2 Peter I Lelkes,1 Giora Feuerstein1,2 1Department of Bioengineering, College of Engineering, Temple University, Philadelphia, 2Debina Diagnostic, Inc., Newton Square, PA, USA Abstract: Thromboembolic events (TEE) underwrite key causes of death in developed countries. While advanced imaging technologies such as computed tomography scans serve to diagnose blood clots during acute cardiovascular events, no such technology is available in routine primary care for TEE risk assessment. Here, we describe an imaging platform technology based on bioengineered fluorescent nanodiamond particles (F-NDPs) functionalized with bitistatin (Bit), a disintegrin that specifically binds to the αIIbβ3 integrin, platelet fibrinogen receptor (PFR) on activated platelets. Covalent linkage of purified Bit to F-NDP was concentration-dependent and saturable, as validated by enzyme-linked immunosorbent assay using specific anti-Bit antibodies. F-NDP–Bit interacted with purified PFR, either in immobilized or soluble form. Lotrafiban, a nonpeptide, αIIbβ3 receptor antagonist, specifically blocked F-NDP–Bit–PFR complex formation. Moreover, F-NDP–Bit specifically binds to activated platelets incorporated into a clot generated by thrombin-activated rat platelet-rich plasma (PRP). Our results suggest that engineered F-NDP–Bit particles could serve as noninvasive, “real-time” optical diagnostics for clots present in blood vessels. Keywords: carbon nanoparticles, blood clots, imaging, platelet fibrinogen receptor, fluorescence, disintegrin, thromboembolic complications, thrombosisMarcinkiewicz CGerstenhaber JASternberg MLelkes PIFeuerstein GDove Medical Pressarticlecarbon nanoparticlesnanodiamond particlesblood clotsimagingplatelet fibrinogen receptorfluorescencedisintegrin.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 3711-3720 (2017)
institution DOAJ
collection DOAJ
language EN
topic carbon nanoparticles
nanodiamond particles
blood clots
imaging
platelet fibrinogen receptor
fluorescence
disintegrin.
Medicine (General)
R5-920
spellingShingle carbon nanoparticles
nanodiamond particles
blood clots
imaging
platelet fibrinogen receptor
fluorescence
disintegrin.
Medicine (General)
R5-920
Marcinkiewicz C
Gerstenhaber JA
Sternberg M
Lelkes PI
Feuerstein G
Bitistatin-functionalized fluorescent nanodiamond particles specifically bind to purified human platelet integrin receptor αIIbβ3 and activated platelets
description Cezary Marcinkiewicz,1,2 Jonathan A Gerstenhaber,1 Mark Sternberg,2 Peter I Lelkes,1 Giora Feuerstein1,2 1Department of Bioengineering, College of Engineering, Temple University, Philadelphia, 2Debina Diagnostic, Inc., Newton Square, PA, USA Abstract: Thromboembolic events (TEE) underwrite key causes of death in developed countries. While advanced imaging technologies such as computed tomography scans serve to diagnose blood clots during acute cardiovascular events, no such technology is available in routine primary care for TEE risk assessment. Here, we describe an imaging platform technology based on bioengineered fluorescent nanodiamond particles (F-NDPs) functionalized with bitistatin (Bit), a disintegrin that specifically binds to the αIIbβ3 integrin, platelet fibrinogen receptor (PFR) on activated platelets. Covalent linkage of purified Bit to F-NDP was concentration-dependent and saturable, as validated by enzyme-linked immunosorbent assay using specific anti-Bit antibodies. F-NDP–Bit interacted with purified PFR, either in immobilized or soluble form. Lotrafiban, a nonpeptide, αIIbβ3 receptor antagonist, specifically blocked F-NDP–Bit–PFR complex formation. Moreover, F-NDP–Bit specifically binds to activated platelets incorporated into a clot generated by thrombin-activated rat platelet-rich plasma (PRP). Our results suggest that engineered F-NDP–Bit particles could serve as noninvasive, “real-time” optical diagnostics for clots present in blood vessels. Keywords: carbon nanoparticles, blood clots, imaging, platelet fibrinogen receptor, fluorescence, disintegrin, thromboembolic complications, thrombosis
format article
author Marcinkiewicz C
Gerstenhaber JA
Sternberg M
Lelkes PI
Feuerstein G
author_facet Marcinkiewicz C
Gerstenhaber JA
Sternberg M
Lelkes PI
Feuerstein G
author_sort Marcinkiewicz C
title Bitistatin-functionalized fluorescent nanodiamond particles specifically bind to purified human platelet integrin receptor αIIbβ3 and activated platelets
title_short Bitistatin-functionalized fluorescent nanodiamond particles specifically bind to purified human platelet integrin receptor αIIbβ3 and activated platelets
title_full Bitistatin-functionalized fluorescent nanodiamond particles specifically bind to purified human platelet integrin receptor αIIbβ3 and activated platelets
title_fullStr Bitistatin-functionalized fluorescent nanodiamond particles specifically bind to purified human platelet integrin receptor αIIbβ3 and activated platelets
title_full_unstemmed Bitistatin-functionalized fluorescent nanodiamond particles specifically bind to purified human platelet integrin receptor αIIbβ3 and activated platelets
title_sort bitistatin-functionalized fluorescent nanodiamond particles specifically bind to purified human platelet integrin receptor αiibβ3 and activated platelets
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/83b9862dbe8d4227bed0ed76381d525c
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