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The Pharmacological Effects of Silver Nanoparticles Functionalized with Eptifibatide on Platelets and Endothelial Cells

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cris.lastimport.scopus2024-02-12T20:48:28Z
dc.abstract.enPurpose: In the search for new drug delivery platforms for cardiovascular diseases and coating of medical devices, we synthesized eptifibatide-functionalized silver nanoparticles (AgNPs-EPI) and examined the pharmacological activity of AgNPs-EPI on platelets and endothelial cells in vitro and ex vivo. Methods: Spherical AgNPs linked to eptifibatide were synthesized and characterized. Cytotoxicity was measured in microvascular endothelial cells (HMEC-1), platelets and red blood cells. Platelet mitochondrial respiration was measured using the Oxygraph-2k, a high-resolution modular respirometry system. The effect of AgNPs-EPI on the aggregation of washed platelets was measured by light aggregometry and the ex vivo occlusion time was determined using a reference laboratory method. The surface amount of platelet receptors such as P-selectin and GPIIb/IIIa was measured. The influence of AgNPS-EPI on blood coagulation science was assessed. Finally, the effect of AgNPs-EPI on endothelial cells was measured by the levels of 6-keto-PGF1alpha, tPa, cGMP and vWF. Results: We describe the synthesis of AgNPs using eptifibatide as the stabilizing ligand. The molecules of this drug are directly bonded to the surface of the nanoparticles. The synthesized AgNPs-EPI did not affect the viability of platelets, endothelial cells and erythrocytes. Preincubation of platelets with AgNPs-EPI protected by mitochondrial oxidative phosphorylation capacity. AgNPs-EPI inhibited aggregation-induced P-selectin expression and GPIIb/IIIa conformational changes in platelets. AgNPs-EPI caused prolonga-tion of the occlusion time in the presence of collagen/ADP and collagen/adrenaline. AgNPs-EPI regulated levels of 6-keto-PGF1alpha, tPa, vWf and cGMP produced in thrombin stimulated HMEC-1 cells. Conclusion: AgNPs-EPI show anti-aggregatory activity at concentrations lower than those required by the free drug acting via regulation of platelet aggregation, blood coagulation, and endothelial cell activity. Our results provide proof-of-principle evidence that AgNPs may be used as an effective delivery platform for antiplatelet drugs.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorInkielewicz-Stepniak, Iwona
dc.contributor.authorSantos-Martinez, Maria Jose
dc.contributor.authorRadomski, Marek Witold
dc.contributor.authorCieciórski, Piotr
dc.contributor.authorMegiel, Elżbieta
dc.contributor.authorFlis, Damian
dc.contributor.authorSzczoczarz, Anna
dc.contributor.authorIwicka, Eliza
dc.contributor.authorHajtuch, Justyna
dc.date.accessioned2024-01-26T10:29:50Z
dc.date.available2024-01-26T10:29:50Z
dc.date.copyright2022-09-19
dc.date.issued2022
dc.description.accesstimeAT_PUBLICATION
dc.description.financePublikacja bezkosztowa
dc.description.versionFINAL_PUBLISHED
dc.description.volumeVolume 17
dc.identifier.doi10.2147/IJN.S373691
dc.identifier.issn1176-9114
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/122812
dc.identifier.weblinkhttps://www.dovepress.com/getfile.php?fileID=84021
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofInternational journal of nanomedicine
dc.relation.pages4383-4400
dc.rightsCC-BY-NC
dc.sciencecloudnosend
dc.subject.enaggregation
dc.subject.enantiplatelet
dc.subject.enbiocompatibility
dc.subject.encoagulation system
dc.subject.endrug delivery
dc.subject.enRGD
dc.titleThe Pharmacological Effects of Silver Nanoparticles Functionalized with Eptifibatide on Platelets and Endothelial Cells
dc.typeJournalArticle
dspace.entity.typePublication