The cell-type specific uptake of polymer-coated or micelle-embedded QDs and SPIOs does not provoke an acute pro-inflammatory response in the liver
Semiconductor quantum dots (QD) and superparamagnetic iron oxide nanocrystals (SPIO) have exceptional physical properties that are well suited for biomedical applications in vitro and in vivo. For future applications, the direct injection of nanocrystals for imaging and therapy represents an importa...
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Format: | Article |
Language: | English |
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Beilstein-Institut
2014-09-01
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Series: | Beilstein Journal of Nanotechnology |
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Online Access: | https://doi.org/10.3762/bjnano.5.155 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Markus Heine Alexander Bartelt Oliver T. Bruns Denise Bargheer Artur Giemsa Barbara Freund Ludger Scheja Christian Waurisch Alexander Eychmüller Rudolph Reimer Horst Weller Peter Nielsen Joerg Heeren |
spellingShingle |
Markus Heine Alexander Bartelt Oliver T. Bruns Denise Bargheer Artur Giemsa Barbara Freund Ludger Scheja Christian Waurisch Alexander Eychmüller Rudolph Reimer Horst Weller Peter Nielsen Joerg Heeren The cell-type specific uptake of polymer-coated or micelle-embedded QDs and SPIOs does not provoke an acute pro-inflammatory response in the liver Beilstein Journal of Nanotechnology hepatocytes inflammation Kupffer cells liver sinusoidal endothelial cells nanoparticle toxicity nanoparticle uptake quantum dots superparamagnetic iron-oxide nanocrystals |
author_facet |
Markus Heine Alexander Bartelt Oliver T. Bruns Denise Bargheer Artur Giemsa Barbara Freund Ludger Scheja Christian Waurisch Alexander Eychmüller Rudolph Reimer Horst Weller Peter Nielsen Joerg Heeren |
author_sort |
Markus Heine |
title |
The cell-type specific uptake of polymer-coated or micelle-embedded QDs and SPIOs does not provoke an acute pro-inflammatory response in the liver |
title_short |
The cell-type specific uptake of polymer-coated or micelle-embedded QDs and SPIOs does not provoke an acute pro-inflammatory response in the liver |
title_full |
The cell-type specific uptake of polymer-coated or micelle-embedded QDs and SPIOs does not provoke an acute pro-inflammatory response in the liver |
title_fullStr |
The cell-type specific uptake of polymer-coated or micelle-embedded QDs and SPIOs does not provoke an acute pro-inflammatory response in the liver |
title_full_unstemmed |
The cell-type specific uptake of polymer-coated or micelle-embedded QDs and SPIOs does not provoke an acute pro-inflammatory response in the liver |
title_sort |
cell-type specific uptake of polymer-coated or micelle-embedded qds and spios does not provoke an acute pro-inflammatory response in the liver |
publisher |
Beilstein-Institut |
series |
Beilstein Journal of Nanotechnology |
issn |
2190-4286 |
publishDate |
2014-09-01 |
description |
Semiconductor quantum dots (QD) and superparamagnetic iron oxide nanocrystals (SPIO) have exceptional physical properties that are well suited for biomedical applications in vitro and in vivo. For future applications, the direct injection of nanocrystals for imaging and therapy represents an important entry route into the human body. Therefore, it is crucial to investigate biological responses of the body to nanocrystals to avoid harmful side effects. In recent years, we established a system to embed nanocrystals with a hydrophobic oleic acid shell either by lipid micelles or by the amphiphilic polymer poly(maleic anhydride-alt-1-octadecene) (PMAOD). The goal of the current study is to investigate the uptake processes as well as pro-inflammatory responses in the liver after the injection of these encapsulated nanocrystals. By immunofluorescence and electron microscopy studies using wild type mice, we show that 30 min after injection polymer-coated nanocrystals are primarily taken up by liver sinusoidal endothelial cells. In contrast, by using wild type, Ldlr-/- as well as Apoe-/- mice we show that nanocrystals embedded within lipid micelles are internalized by Kupffer cells and, in a process that is dependent on the LDL receptor and apolipoprotein E, by hepatocytes. Gene expression analysis of pro-inflammatory markers such as tumor necrosis factor alpha (TNFα) or chemokine (C-X-C motif) ligand 10 (Cxcl10) indicated that 48 h after injection internalized nanocrystals did not provoke pro-inflammatory pathways. In conclusion, internalized nanocrystals at least in mouse liver cells, namely endothelial cells, Kupffer cells and hepatocytes are at least not acutely associated with potential adverse side effects, underlining their potential for biomedical applications. |
topic |
hepatocytes inflammation Kupffer cells liver sinusoidal endothelial cells nanoparticle toxicity nanoparticle uptake quantum dots superparamagnetic iron-oxide nanocrystals |
url |
https://doi.org/10.3762/bjnano.5.155 |
work_keys_str_mv |
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doaj-55e9ac29353c453c8bd6ba64f8fa1cd22020-11-24T23:14:19ZengBeilstein-InstitutBeilstein Journal of Nanotechnology2190-42862014-09-01511432144010.3762/bjnano.5.1552190-4286-5-155The cell-type specific uptake of polymer-coated or micelle-embedded QDs and SPIOs does not provoke an acute pro-inflammatory response in the liverMarkus Heine0Alexander Bartelt1Oliver T. Bruns2Denise Bargheer3Artur Giemsa4Barbara Freund5Ludger Scheja6Christian Waurisch7Alexander Eychmüller8Rudolph Reimer9Horst Weller10Peter Nielsen11Joerg Heeren12Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf; Martinistrasse 52, 20246 Hamburg, GermanyDepartment of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf; Martinistrasse 52, 20246 Hamburg, GermanyDepartment of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf; Martinistrasse 52, 20246 Hamburg, GermanyDepartment of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf; Martinistrasse 52, 20246 Hamburg, GermanyDepartment of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf; Martinistrasse 52, 20246 Hamburg, GermanyDepartment of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf; Martinistrasse 52, 20246 Hamburg, GermanyDepartment of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf; Martinistrasse 52, 20246 Hamburg, GermanyInstitute of Physical Chemistry and Electrochemistry, Technical University of Dresden, 01062 Dresden, GermanyInstitute of Physical Chemistry and Electrochemistry, Technical University of Dresden, 01062 Dresden, GermanyDepartment of Electron Microscopy and Micro Technology, Heinrich-Pette Institute, Martinistrasse 52, 20246 Hamburg, GermanyInstitute of Physical Chemistry, University of Hamburg, Grindelallee 117, 20146 Hamburg, GermanyDepartment of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf; Martinistrasse 52, 20246 Hamburg, GermanyDepartment of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf; Martinistrasse 52, 20246 Hamburg, GermanySemiconductor quantum dots (QD) and superparamagnetic iron oxide nanocrystals (SPIO) have exceptional physical properties that are well suited for biomedical applications in vitro and in vivo. For future applications, the direct injection of nanocrystals for imaging and therapy represents an important entry route into the human body. Therefore, it is crucial to investigate biological responses of the body to nanocrystals to avoid harmful side effects. In recent years, we established a system to embed nanocrystals with a hydrophobic oleic acid shell either by lipid micelles or by the amphiphilic polymer poly(maleic anhydride-alt-1-octadecene) (PMAOD). The goal of the current study is to investigate the uptake processes as well as pro-inflammatory responses in the liver after the injection of these encapsulated nanocrystals. By immunofluorescence and electron microscopy studies using wild type mice, we show that 30 min after injection polymer-coated nanocrystals are primarily taken up by liver sinusoidal endothelial cells. In contrast, by using wild type, Ldlr-/- as well as Apoe-/- mice we show that nanocrystals embedded within lipid micelles are internalized by Kupffer cells and, in a process that is dependent on the LDL receptor and apolipoprotein E, by hepatocytes. Gene expression analysis of pro-inflammatory markers such as tumor necrosis factor alpha (TNFα) or chemokine (C-X-C motif) ligand 10 (Cxcl10) indicated that 48 h after injection internalized nanocrystals did not provoke pro-inflammatory pathways. In conclusion, internalized nanocrystals at least in mouse liver cells, namely endothelial cells, Kupffer cells and hepatocytes are at least not acutely associated with potential adverse side effects, underlining their potential for biomedical applications.https://doi.org/10.3762/bjnano.5.155hepatocytesinflammationKupffer cellsliver sinusoidal endothelial cellsnanoparticle toxicitynanoparticle uptakequantum dotssuperparamagnetic iron-oxide nanocrystals |