- Full (HTML) - Full (PDF) - Related EHP Articles - PubMed:Related Articles - PubMed:Citation - Cited in PMC - Purchase This Issue

Jorina Geys,¹ Abderrahim Nemmar,^1,2 Erik Verbeken,³ Erik Smolders,⁴ Monica Ratoi,⁵ Marc F. Hoylaerts,⁶ Benoit Nemery,¹ and Peter H.M. Hoet¹

¹Laboratory of Pneumology, Unit for Lung Toxicology, Katholieke Universiteit Leuven, Leuven, Belgium; ²Faculty of Medicine and Health Sciences, Department of Physiology, United Arab Emirates University, Al-ain, United Arab Emirates; ³Department of Pathology, Universitaire Ziekenhuizen Leuven, Leuven, Belgium; ⁴Laboratory of Soil and Water Management, Katholieke Universiteit Leuven, Leuven, Belgium; ⁵Department of Materials, University of Oxford, Oxford, United Kingdom; ⁶Center for Molecular and Vascular Biology, Katholieke Universiteit Leuven, Leuven, Belgium

Abstract
Background: Quantum dots (QDs) have numerous possible applications for in vivo imaging. However, toxicity data are scarce.

Objectives: To determine the acute in vivo toxicity of QDs with carboxyl surface coating (carboxyl-QDs) and QDs with amine surface coating (amine-QDs) , we investigated the inflammatory properties, tissue distribution, and prothrombotic effects after intravenous injection.

Methods: We performed particle characterization by transmission electron microscopy and dynamic light scattering. Carboxyl-QDs and amine-QDs were intravenously injected in mice (1.44–3,600 pmol/mouse) . At different time intervals, analyses included fluorescence microscopy, blood cell analysis, bronchoalveolar lavage, wet and dry organ weights, and cadmium concentration in various organs. We examined the prothrombotic effects in vivo by assessing the effect of pretreatment with the anticoagulant heparin and by measuring platelet activation (P-selectin) , and in vitro by platelet aggregation in murine and human platelet-rich plasma exposed to QDs (1.44–1,620 pmol/mL) .

Results: At doses of 3,600 and 720 pmol/mouse, QDs caused marked vascular thrombosis in the pulmonary circulation, especially with carboxyl-QDs. We saw an effect of surface charge for all the parameters tested. QDs were mainly found in lung, liver, and blood. Thrombotic complications were abolished, and P-selectin was not affected by pretreatment of the animals with heparin. In vitro, carboxyl-QDs and amine-QDs enhanced adenosine-5´-diphosphate–induced platelet aggregation.

Conclusion: At high doses, QDs caused pulmonary vascular thrombosis, most likely by activating the coagulation cascade via contact activation. Our study highlights the need for careful safety evaluation of QDs before their use in human applications. Furthermore, it is clear that surface charge is an important parameter in nanotoxicity.

Key words: blood cell analysis, coagulation, intravenous, in vivo, nanoparticles, platelet aggregation, quantum dots, surface charge, thrombosis, toxicity. Environ Health Perspect 116:1607–1613 (2008) .  doi:10.1289/ehp.11566 available via http://dx.doi.org/ [Online 18 July 2008]

Address correspondence to P.H.M. Hoet, K.U. Leuven, Laboratory of Pneumology, Unit for Lung Toxicology, Herestraat 49 O&N1 bus 706, 3000 Leuven, Belgium. Telephone: 32-16-330197. Fax: 32-16-347124. E-mail: peter.hoet@med.kuleuven.be

We thank S. Van kerckhoven, J. Buekers, and K. Coorevits for their technical assistance.

This study was supported by a grant from FWO-Flanders (G.0169.04) and received financial support of the European Commission through the Sixth Framework Programme for Research and Technological Development (NMP2-CT-2005-515843 contract "NANOSAFE2") .

The authors declare they have no competing financial interests.

Received 10 April 2008 ; accepted 18 July 2008.