Back to Journals » International Journal of Nanomedicine » Volume 7

Amorphous silica nanoparticles aggregate human platelets: potential implications for vascular homeostasis

Authors Corbalan JJ, Medina C, Jacoby, Malinski , Radomskic M 

Received 16 November 2011

Accepted for publication 17 December 2011

Published 7 February 2012 Volume 2012:7 Pages 631—639


Review by Single anonymous peer review

Peer reviewer comments 3

J Jose Corbalan1,2, Carlos Medina1, Adam Jacoby2, Tadeusz Malinski2, Marek W Radomski1
1School of Pharmacy and Pharmaceutical Sciences, Faculty of Health Sciences, Panoz Institute, Trinity College Dublin, Ireland; 2Department of Chemistry and Biochemistry, Ohio University, Athens, OH, USA

Background: Amorphous silica nanoparticles (SiNP) can be used in medical technologies and other industries leading to human exposure. However, an increased number of studies indicate that this exposure may result in cardiovascular inflammation and damage. A high ratio of nitric oxide to peroxynitrite concentrations ([NO]/[ONOO-]) is crucial for cardiovascular homeostasis and platelet hemostasis. Therefore, we studied the influence of SiNP on the platelet [NO]/[ONOO-] balance and platelet aggregation.
Methods: Nanoparticle–platelet interaction was examined using transmission electron microscopy. Electrochemical nanosensors were used to measure the levels of NO and ONOO- released by platelets upon nanoparticle stimulation. Platelet aggregation was studied using light aggregometry, flow cytometry, and phase contrast microscopy.
Results: Amorphous SiNP induced NO release from platelets followed by a massive stimulation of ONOO- leading to an unfavorably low [NO]/[ONOO-] ratio. In addition, SiNP induced an upregulation of selectin P expression and glycoprotein IIb/IIIa activation on the platelet surface membrane, and led to platelet aggregation via adenosine diphosphate and matrix metalloproteinase 2-dependent mechanisms. Importantly, all the effects on platelet aggregation were inversely proportional to nanoparticle size.
Conclusions: The exposure of platelets to amorphous SiNP induces a critically low [NO]/[ONOO-] ratio leading to platelet aggregation. These findings provide new insights into the pharmacological profile of SiNP in platelets.

Keywords: amorphous silica nanoparticles, nanotoxicology, nitric oxide, peroxynitrite, platelet aggregation

Creative Commons License © 2012 The Author(s). This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.