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 microg ml(-1)) were investigated. Nanoparticles were compared with standard urban
particulate matter (SRM1648, average size 1.4 microm). 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 (MCN>or=SWNT>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.