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Pharmacological characterization of nanoparticle-induced platelet microaggregation using quartz crystal microbalance with dissipation: comparison with light aggregometry

Authors Santos-Martinez MJ, Tomaszewski KA, Medina C, Bazou D, Gilmer JF, Radomski MW

Received 10 March 2015

Accepted for publication 28 April 2015

Published 13 August 2015 Volume 2015:10(1) Pages 5107—5119

DOI https://doi.org/10.2147/IJN.S84305

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Thomas J Webster

Maria J Santos-Martinez,1,2,* Krzysztof A Tomaszewski,1,3,* Carlos Medina,1 Despina Bazou,4 John F Gilmer,1 Marek W Radomski1,5,6

1School of Pharmacy and Pharma­ceutical Sciences and Trinity Biomedical Sciences Institute, 2School of Medicine, Trinity College Dublin, University of Dublin, Dublin, Ireland; 3Department of Anatomy, Jagiellonian University Medical College, Krakow, Poland; 4Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA; 5Kardio-Med Silesia, Zabrze, 6Medical University of Silesia, Katowice, Poland

*These authors contributed equally to this paper

Background: Engineered nanoparticles (NPs) can induce platelet activation and aggregation, but the mechanisms underlying these interactions are not well understood. This could be due in part to use of devices that study platelet function under quasi-static conditions with low sensitivity to measure platelet microaggregation. Therefore, in this study we investigated the pharmacological pathways and regulators of NP-induced platelet microaggregation under flow conditions at nanoscale using quartz crystal microbalance with dissipation (QCM-D) and compared the data thus obtained with those generated by light aggregometry.
Methods: Blood was collected from healthy volunteers, and platelet-rich plasma was obtained. Thrombin receptor-activating peptide, a potent stimulator of platelet function, and pharmacological inhibitors were used to modulate platelet microaggregation in the presence/absence of silica (10 nm and 50 nm) and polystyrene (23 nm) NPs. Light aggregometry was used to study platelet aggregation in macroscale. Optical, immunofluorescence, and scanning electron microscopy were also used to visualize platelet aggregates.
Results: Platelet microaggregation was enhanced by thrombin receptor-activating peptide, whereas prostacyclin, nitric oxide donors, acetylsalicylic acid, and phenanthroline, but not adenosine diphosphate (ADP) blockers, were able to inhibit platelet microaggregation. NPs caused platelet microaggregation, an effect not detectable by light aggregometry. NP-induced microaggregation was attenuated by platelet inhibitors.
Conclusion: NP-induced platelet microaggregation appears to involve classical proaggregatory pathways (thromboxane A2-mediated and matrix metalloproteinase-2-mediated) and can be regulated by endogenous (prostacyclin) and pharmacological (acetylsalicylic acid, phenanthroline, and nitric oxide donors) inhibitors of platelet function. Quartz crystal microbalance with dissipation, but not light aggregometry, is an appropriate method for studying NP-induced microaggregation.

Keywords: platelet microaggregation, quartz crystal microbalance with dissipation, pharmacology, nanoparticles

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