Document Detail


Cellular uptake mechanisms and toxicity of quantum dots in dendritic cells.
MedLine Citation:
PMID:  21793671     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Quantum dots (QDs) are nanoparticles with strong fluorescent emission and are novel tools used in biomedical applications, but the toxicity and mechanism of cellular uptake are poorly understood. QD655-COOH (negative charge, 18 nm) consist of a cadmium/selenide core and a zinc sulfide shell with a carboxylic acid coating with an emission wavelength of 655 nm. Materials & Methods: Peripheral blood mononuclear cells were isolated from porcine blood by gradient centrifugation, and monocytes, which are CD14 positive, were purified. Monocytes were differentiated into dendritic cells (DCs) with GM-CSF and IL-4. Results: Monocytes showed cellular uptake of QD655-COOH, while lymphocytes did not. Monocyte differentiation into DCs increased the cellular uptake by sixfold when dosed with 2 nM of QD655-COOH. Transmission electron microscopy depicted QD655-COOH in the cytoplasmic vacuoles of DCs. Twelve endocytic inhibitors demonstrated QD655-COOH endocytosis in DCs, which was recognized by clathrin and scavenger receptors and regulated by F-actin and phospholipase C. In addition, DC maturation with lipopolysaccharide (LPS) caused an increase in QD655-COOH uptake compared with DCs without LPS stimulation. Viability assays, including 96AQ, CCK-8, alamar blue and ApoTox, exhibited minimal toxicity in DCs dosed with QD655-COOH at 24 h. However, glutathione levels showed a significant decrease with 10 nM of QD655-COOH. Finally, QD655-COOH exposure was associated with a decrease in CD80/CD86 expression after LPS stimulation, suggesting suppression with DC maturation. Conclusion: These findings shed light on the mechanism of QD655-COOH uptake in DCs and that cellular uptake pathways are dependent on cell type and cell differentiation.
Authors:
Leshuai W Zhang; Wolfgang Bäumer; Nancy A Monteiro-Riviere
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Nanomedicine (London, England)     Volume:  6     ISSN:  1748-6963     ISO Abbreviation:  Nanomedicine (Lond)     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-28     Completed Date:  2011-12-05     Revised Date:  2012-05-02    
Medline Journal Info:
Nlm Unique ID:  101278111     Medline TA:  Nanomedicine (Lond)     Country:  England    
Other Details:
Languages:  eng     Pagination:  777-91     Citation Subset:  IM    
Affiliation:
Center for Chemical Toxicology Research & Pharmacokinetics, North Carolina State University, Raleigh, NC 27606, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD80 / immunology
Antigens, CD86 / immunology
Cell Differentiation
Cell Survival
Cells, Cultured
Dendritic Cells / cytology*,  immunology
Endocytosis*
Granulocyte-Macrophage Colony-Stimulating Factor / immunology
Lipopolysaccharides / immunology
Monocytes / cytology,  immunology
Quantum Dots*
Swine
Grant Support
ID/Acronym/Agency:
R01 ES016138/ES/NIEHS NIH HHS; R01 ES016138-01/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD80; 0/Antigens, CD86; 0/Lipopolysaccharides; 83869-56-1/Granulocyte-Macrophage Colony-Stimulating Factor

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