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Text
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<a href="http://doi.org/10.1016/j.biomaterials.2007.12.015" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.biomaterials.2007.12.015</a>
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Pages
1676-1685
Issue
11
Volume
29
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Title
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Affinity Manipulation Of Surface-conjugated Rgd Peptide To Modulate Binding Of Liposomes To Activated Platelets
Publisher
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Biomaterials
Date
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2008
2008-04
Subject
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cyclic RGD; delivery systems; drug-eluting stents; Engineering; insight; integrin alpha(iib)beta(3); liposomes; Materials Science; nanoparticles; peptide modification; platelet-targeting; responses; restenosis; therapy
Creator
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Huang G F; Zhou Z M; Srinivasan R; Penn M S; Kottke-Marchant K; Marchant R E; Gupta A S
Description
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Platelet adhesion, activation and fibrinogen-mediated aggregation are primary events in vascular thrombosis and occlusion. An injectable delivery system that can carry thrombolytics selectively to the sites of active platelet aggregation has immense potential in minimally invasive targeted therapy of vascular occlusion. To this end we are studying liposomes surface-modified by fibrinogen-mimetic RGD motifs that can selectively target and bind integrin GPIIb-IIIa on activated platelets. Here we report liposome surface-modification with a conformationally constrained high affinity cyclic RGD motif to modulate the GPIIb-IIIa-binding capability of the liposomes. Such affinity enhancement is important for practical in vivo applications to compete with native fibrinogen towards binding GPIIb-IIIa. The platelet-binding of RGD-modified liposomes was studied by fluorescence and scanning electron microscopy, and flow cytometry, in vitro. Binding of RGD-modified liposomes was also tested in vivo in a rat carotid injury model and analyzed ex vivo by fluorescence microscopy. The results from all experiments show that cyclic RGD-liposomes bind activated platelets significantly higher compared to linear RGD-liposomes. Hence, the results establish the feasibility of modulating the platelet-targeting and binding ability of vascularly targeted liposomes by manipulating the affinity of surface-modifying ligands. (c) 2008 Elsevier Ltd. All rights reserved.
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<a href="http://doi.org/10.1016/j.biomaterials.2007.12.015" target="_blank" rel="noreferrer noopener">10.1016/j.biomaterials.2007.12.015</a>
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Journal Article or Conference Abstract Publication
2008
Biomaterials
cyclic RGD
delivery systems
Drug-Eluting Stents
Engineering
Gupta A S
Huang G F
insight
integrin alpha(iib)beta(3)
Journal Article or Conference Abstract Publication
Kottke-Marchant K
liposomes
Marchant R E
Materials Science
Nanoparticles
Penn M S
peptide modification
platelet-targeting
responses
Restenosis
Srinivasan R
therapy
Zhou Z M