title: Pharmacological characterization of nanoparticle-induced platelet microaggregation using quartz crystal microbalance with dissipation: comparison with light aggregometry.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, University of Dublin, Dublin, Ireland ; School of Medicine, Trinity College Dublin, University of Dublin, Dublin, Ireland.
authors: Maria J
authors: MJ
authors: Santos-Martinez
authors: School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, University of Dublin, Dublin, Ireland ; Department of Anatomy, Jagiellonian University Medical College, Krakow, Poland.
authors: Krzysztof A
authors: KA
authors: Tomaszewski
authors: School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, University of Dublin, Dublin, Ireland.
authors: Carlos
authors: C
authors: Medina
authors: Edwin L Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors: Despina
authors: D
authors: Bazou
authors: School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, University of Dublin, Dublin, Ireland.
authors: John F
authors: JF
authors: Gilmer
authors: School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, University of Dublin, Dublin, Ireland ; Kardio-Med Silesia, Zabrze, Poland ; Medical University of Silesia, Katowice, Poland.
authors: Marek W
authors: MW
authors: Radomski
mesh_terms: D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects; D002478:Cells, Cultured; D003029:Coagulants / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D010974:Platelet Aggregation / Q000187:drug effects*; D058525:Quartz Crystal Microbalance Techniques / Q000379:methods*
chemical_list: D003029:Coagulants
keywords: nanoparticles; pharmacology; platelet microaggregation; quartz crystal microbalance with dissipation