Nanoparticle‐induced platelet aggregation and vascular thrombosis

Abstract

Ever increasing use of engineered carbon nanoparticles in nanopharmacology for selective imaging, sensor or drug delivery systems has increased the potential for blood platelet–nanoparticle interactions. We studied the effects of engineered and combustion‐derived carbon nanoparticles on human platelet aggregation in vitro and rat vascular thrombosis in vivo. Multiplewall (MWNT), singlewall (SWNT) nanotubes, C60 fullerenes (C60CS) and mixed carbon nanoparticles (MCN) (0.2–300 μ g ml−1) were investigated. Nanoparticles were compared with standard urban particulate matter (SRM1648, average size 1.4 μ m). Platelet function was studied using lumi aggregometry, phase‐contrast, immunofluorescence and transmission electron microscopy, flow cytometry, zymography and pharmacological inhibitors of platelet aggregation. Vascular thrombosis was induced by ferric chloride and the rate of thrombosis was measured, in the presence of carbon particles, with an ultrasonic flow probe. Carbon particles, except C60CS, stimulated platelet aggregation (MCNSWNT>MWNT>SRM1648) and accelerated the rate of vascular thrombosis in rat carotid arteries with a similar rank order of efficacy. All particles resulted in upregulation of GPIIb/IIIa in platelets. In contrast, particles differentially affected the release of platelet granules, as well as the activity of thromboxane‐, ADP, matrix metalloproteinase‐ and protein kinase C‐dependent pathways of aggregation. Furthermore, particle‐induced aggregation was inhibited by prostacyclin and S‐nitroso‐glutathione, but not by aspirin. Thus, some carbon nanoparticles and microparticles have the ability to activate platelets and enhance vascular thrombosis. These observations are of importance for the pharmacological use of carbon nanoparticles and pathology of urban particulate matter. British Journal of Pharmacology (2005) 146, 882–893. doi:10.1038/sj.bjp.0706386