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An in vitro study of vascular endothelial toxicity of CdTe quantum dots
Department of Life Science and Biomedical Engineering, Zhejiang.
Department of Life Science and Biomedical Engineering, Zhejiang.
Department of Life Science and Biomedical Engineering, Zhejiang.
Centre for Optical and Electromagnetic Research, Zhejiang University.
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2011 (English)In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 282, no 3, 94-103 p.Article in journal (Refereed) Published
Abstract [en]

Quantum dots (QDs), as novel bioimaging and drug delivery agents, are generally introduced into vascular system by injection, and thus directly exposed to vascular endothelial cells (ECs). However, the adverse effects of QDs on ECs are poorly understood. In this study, employing human umbilical vein ECs (HUVECs), we investigated the potential vascular endothelial toxicity of mercaptosuccinic acid (MSA)-capped CdTe QDs in vitro. In the experiment, water-soluble and pH stable CdTe QDs were synthesized; and the cell viability assays showed that CdTe QDs (0.1-100 mu g/mL) dose-dependently decreased the cell viability of HUVECs, indicating CdTe QDs induced significant endothelial toxicity. The flow cytometric and immunofluorescence results revealed that 10 mu g/mL CdTe QDs elicited significant oxidative stress, mitochondrial network fragmentation as well as disruption of mitochondrial membrane potential (Delta psi(m)); whereas ROS scavenger could protect HUVECs from QDs-induced mitochondrial dysfunction. Moreover, upon 24h exposure to 10 mu g/mL CdTe QDs, the apoptotic HUVECs dramatically increased by 402.01%, accompanied with alternative expression of apoptosis proteins, which were upregulation of Bax, down-regulation of Bcl-2, release of mitochondrial cytochrome c and cleavage of caspase-9/caspase-3. These results suggested that CdTe QDs could not only impair mitochondria but also exert endothelial toxicity through activation of mitochondrial death pathway and induction of endothelial apoptosis. Our results provide strong evidences of the direct toxic effects of QDs on human vascular ECs, and reveal that exposure to QDs is a significant risk for the development of cardiovascular diseases. These results also provide helpful guidance on the future safe use and manipulation of QDs to make them more suitable tools in nanomedicine.

Place, publisher, year, edition, pages
Elsevier , 2011. Vol. 282, no 3, 94-103 p.
Keyword [en]
Quantum dots, Vascular endothelial cells, Apoptosi, s Mitochondrial dysfunction, Reactive oxygen species
National Category
Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:kth:diva-33317DOI: 10.1016/j.tox.2011.01.015ISI: 000289327500004PubMedID: 21291946ScopusID: 2-s2.0-79952314659OAI: oai:DiVA.org:kth-33317DiVA: diva2:414537
Available from: 2011-05-03 Created: 2011-05-03 Last updated: 2011-09-08Bibliographically approved
In thesis
1. Rational design of nanoparticles for biomedical imaging and photovoltaic applications
Open this publication in new window or tab >>Rational design of nanoparticles for biomedical imaging and photovoltaic applications
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis aims to rationally design nanoparticles and promote their applications in biomedical imaging and photovoltaic cells.

Quantum dots (QDs) are promising fluorescent probes for biomedical imaging. We have fabricated two types of MSA capped QDs: CdTe/ZnSe core/shell QDs synthesized via an aqueous method and CdTe QDs via a hydrothermal method. They present high quantum yields (QYs), narrow emission band widths, high photo- and pH-stability, and low cytotoxicity. QD-IgG probes were produced and applied for labeling breast cancer marker HER2 proteins on MCF-7 cells.

For the purpose of single molecule tracking using QDs as fluorescent probes, we use small affibodies instead of antibodies to produce QD-affibody probes. Smaller QD-target protein complexes are obtained using a direct immunofluorescence approach. These QD-affibody probes are developed to study the dynamic motion of single HER2 proteins on A431 cell membranes.

Fluorescence blinking in single QDs is harmful for dynamic tracking due to information loss. We have experimentally studied the blinking phenomenon and the mechanism behind. We have discovered an emission bunching effect that two nearby QDs tend to emit light synchronously. The long-range Coulomb potential induced by the negative charge on the QD surface is found to be the major cause for the single QD blinking and the emission bunching in QD pairs.

We have studied the in vitro cytotoxicity of CdTe QDs to human umbilical vein endothelial cells (HUVECs). The QDs treatment increases the intracellular reactive oxygen species (ROS) level and disrupts the mitochondrial membrane potential. The protein expression levels indicate that the mitochondria apoptosis is the main cause of HUVCEs apoptosis induced by CdTe QDs.

Gold nanorods (GNRs) are scattering probes due to their tunable surface plasmon resonance (SPR) enhanced scattering spectrum. In order to control the yield and morphology of GNRs, we have systematically studied the effects of composition and concentration in the growth solution on the quality of the GNRs produced via a seed-mediated method. The aspect ratios of GNRs were found to be linearly depended on the concentration ratio of silver ions and CTAB. The high quality GNRs obtained were adsorbed to COS-7 cell membranes for dark field imaging.

We have rationally designed two types of QDs by wave function engineering so as to improve the efficiency of QD-sensitized solar cells. A reversed type-I CdS/CdSe QD confines excitons in the shell region, whereas a type-II ZnSe/CdS QD separates electrons in the shell and holes in the core. Their absorbed photon-to-current efficiencies (APCE) are as high as 40% and 60% respectively.

In conclusion, rationally designed nanoparticles are proven a high potential for applications as probes in biomedical labeling, imaging and molecule tracking, and as sensitizers for photovoltaic cells.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2011
National Category
Theoretical Chemistry
Identifiers
urn:nbn:se:kth:diva-33346 (URN)978-91-7415-973-8 (ISBN)
Public defence
2011-05-24, FB52, AlbaNova, Roslagstullsbacken, Stockholm, 14:00 (English)
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Note
QC 20110511Available from: 2011-05-11 Created: 2011-05-03 Last updated: 2011-05-11Bibliographically approved

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