Acute toxicity and prothrombotic effects of quantum dots: impact of surface charge
Acute toxicity and prothrombotic effects of quantum dots: impact of surface charge
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.
1607-1613
Geys, Jorina
f191137a-5e7a-430c-88a9-c6d87d13af75
Nemmar, Abderrahim
d5bab717-e629-4683-870e-2c93d6c77b26
Verbeken, Erik
0393eae8-573d-403c-8272-e22886cfe701
Smolders, Erik
30af44ba-a709-4f53-b2ee-e510df3f082c
Ratoi, Monica
cfeffe10-31ca-4630-8399-232c4bc2beff
Hoylaerts, Marc F.
65d22c31-504e-4440-bea7-ded8d8b8e857
Nemery, Benoit
9392d44a-855a-411e-8709-5ebe533ee8d4
Hoet, Peter H.M.
9c9f8b1d-f88e-42fa-a337-d9770d956491
December 2008
Geys, Jorina
f191137a-5e7a-430c-88a9-c6d87d13af75
Nemmar, Abderrahim
d5bab717-e629-4683-870e-2c93d6c77b26
Verbeken, Erik
0393eae8-573d-403c-8272-e22886cfe701
Smolders, Erik
30af44ba-a709-4f53-b2ee-e510df3f082c
Ratoi, Monica
cfeffe10-31ca-4630-8399-232c4bc2beff
Hoylaerts, Marc F.
65d22c31-504e-4440-bea7-ded8d8b8e857
Nemery, Benoit
9392d44a-855a-411e-8709-5ebe533ee8d4
Hoet, Peter H.M.
9c9f8b1d-f88e-42fa-a337-d9770d956491
Geys, Jorina, Nemmar, Abderrahim, Verbeken, Erik, Smolders, Erik, Ratoi, Monica, Hoylaerts, Marc F., Nemery, Benoit and Hoet, Peter H.M.
(2008)
Acute toxicity and prothrombotic effects of quantum dots: impact of surface charge.
Environmental Health Perspectives, 116 (12), .
(doi:10.1289/ehp.11566).
(PMID:19079709)
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.
Text
ehp.11566.pdf
- Version of Record
Restricted to Repository staff only
Request a copy
More information
e-pub ahead of print date: 18 July 2008
Published date: December 2008
Organisations:
Engineering Sciences
Identifiers
Local EPrints ID: 155503
URI: http://eprints.soton.ac.uk/id/eprint/155503
ISSN: 0091-6765
PURE UUID: c72f1445-1f6a-4add-bd78-599cdf1d4d07
Catalogue record
Date deposited: 28 May 2010 08:16
Last modified: 14 Mar 2024 02:55
Export record
Altmetrics
Contributors
Author:
Jorina Geys
Author:
Abderrahim Nemmar
Author:
Erik Verbeken
Author:
Erik Smolders
Author:
Marc F. Hoylaerts
Author:
Benoit Nemery
Author:
Peter H.M. Hoet
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics
