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Marcinkiewicz C , Gerstenhaber JA , Sternberg M , Lelkes PI , Feuerstein G
Bitistatin-functionalized fluorescent nanodiamond particles specifically bind to purified human platelet integrin receptor alphaIIbbeta3 and activated platelets
Int J Nanomedicine. 2017 ;12 :3711-3720
PMID: 28553109    PMCID: PMC5440039    URL: https://www.ncbi.nlm.nih.gov/pubmed/28553109
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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 alphaIIbbeta3 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, alphaIIbbeta3 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.
1178-2013 Marcinkiewicz, Cezary Gerstenhaber, Jonathan A Sternberg, Mark Lelkes, Peter I Feuerstein, Giora Journal Article New Zealand Int J Nanomedicine. 2017 May 15;12:3711-3720. doi: 10.2147/IJN.S134128. eCollection 2017.