Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Heine, Markus, Bartelt, Alexander, Bruns, Oliver T, Bargheer, Denise, Giemsa, Artur, Freund, Barbara, Scheja, Ludger, Waurisch, Christian, Eychmüller, Alexander, Reimer, Rudolph, Weller, Horst, Nielsen, Peter, Heeren, Joerg
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Beilstein-Institut 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4168844/
https://www.ncbi.nlm.nih.gov/pubmed/25247125
http://dx.doi.org/10.3762/bjnano.5.155
_version_ 1782335628326731776
author Heine, Markus
Bartelt, Alexander
Bruns, Oliver T
Bargheer, Denise
Giemsa, Artur
Freund, Barbara
Scheja, Ludger
Waurisch, Christian
Eychmüller, Alexander
Reimer, Rudolph
Weller, Horst
Nielsen, Peter
Heeren, Joerg
author_facet Heine, Markus
Bartelt, Alexander
Bruns, Oliver T
Bargheer, Denise
Giemsa, Artur
Freund, Barbara
Scheja, Ludger
Waurisch, Christian
Eychmüller, Alexander
Reimer, Rudolph
Weller, Horst
Nielsen, Peter
Heeren, Joerg
author_sort Heine, Markus
collection PubMed
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.
format Online
Article
Text
id pubmed-4168844
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Beilstein-Institut
record_format MEDLINE/PubMed
spelling pubmed-41688442014-09-22 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 Heine, Markus Bartelt, Alexander Bruns, Oliver T Bargheer, Denise Giemsa, Artur Freund, Barbara Scheja, Ludger Waurisch, Christian Eychmüller, Alexander Reimer, Rudolph Weller, Horst Nielsen, Peter Heeren, Joerg Beilstein J Nanotechnol Full Research Paper 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. Beilstein-Institut 2014-09-02 /pmc/articles/PMC4168844/ /pubmed/25247125 http://dx.doi.org/10.3762/bjnano.5.155 Text en Copyright © 2014, Heine et al. https://creativecommons.org/licenses/by/2.0https://www.beilstein-journals.org/bjnano/termsThis is an Open Access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The license is subject to the Beilstein Journal of Nanotechnology terms and conditions: (https://www.beilstein-journals.org/bjnano/terms)
spellingShingle Full Research Paper
Heine, Markus
Bartelt, Alexander
Bruns, Oliver T
Bargheer, Denise
Giemsa, Artur
Freund, Barbara
Scheja, Ludger
Waurisch, Christian
Eychmüller, Alexander
Reimer, Rudolph
Weller, Horst
Nielsen, Peter
Heeren, Joerg
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 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_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_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
topic Full Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4168844/
https://www.ncbi.nlm.nih.gov/pubmed/25247125
http://dx.doi.org/10.3762/bjnano.5.155
work_keys_str_mv AT heinemarkus thecelltypespecificuptakeofpolymercoatedormicelleembeddedqdsandspiosdoesnotprovokeanacuteproinflammatoryresponseintheliver
AT barteltalexander thecelltypespecificuptakeofpolymercoatedormicelleembeddedqdsandspiosdoesnotprovokeanacuteproinflammatoryresponseintheliver
AT brunsolivert thecelltypespecificuptakeofpolymercoatedormicelleembeddedqdsandspiosdoesnotprovokeanacuteproinflammatoryresponseintheliver
AT bargheerdenise thecelltypespecificuptakeofpolymercoatedormicelleembeddedqdsandspiosdoesnotprovokeanacuteproinflammatoryresponseintheliver
AT giemsaartur thecelltypespecificuptakeofpolymercoatedormicelleembeddedqdsandspiosdoesnotprovokeanacuteproinflammatoryresponseintheliver
AT freundbarbara thecelltypespecificuptakeofpolymercoatedormicelleembeddedqdsandspiosdoesnotprovokeanacuteproinflammatoryresponseintheliver
AT schejaludger thecelltypespecificuptakeofpolymercoatedormicelleembeddedqdsandspiosdoesnotprovokeanacuteproinflammatoryresponseintheliver
AT waurischchristian thecelltypespecificuptakeofpolymercoatedormicelleembeddedqdsandspiosdoesnotprovokeanacuteproinflammatoryresponseintheliver
AT eychmulleralexander thecelltypespecificuptakeofpolymercoatedormicelleembeddedqdsandspiosdoesnotprovokeanacuteproinflammatoryresponseintheliver
AT reimerrudolph thecelltypespecificuptakeofpolymercoatedormicelleembeddedqdsandspiosdoesnotprovokeanacuteproinflammatoryresponseintheliver
AT wellerhorst thecelltypespecificuptakeofpolymercoatedormicelleembeddedqdsandspiosdoesnotprovokeanacuteproinflammatoryresponseintheliver
AT nielsenpeter thecelltypespecificuptakeofpolymercoatedormicelleembeddedqdsandspiosdoesnotprovokeanacuteproinflammatoryresponseintheliver
AT heerenjoerg thecelltypespecificuptakeofpolymercoatedormicelleembeddedqdsandspiosdoesnotprovokeanacuteproinflammatoryresponseintheliver
AT heinemarkus celltypespecificuptakeofpolymercoatedormicelleembeddedqdsandspiosdoesnotprovokeanacuteproinflammatoryresponseintheliver
AT barteltalexander celltypespecificuptakeofpolymercoatedormicelleembeddedqdsandspiosdoesnotprovokeanacuteproinflammatoryresponseintheliver
AT brunsolivert celltypespecificuptakeofpolymercoatedormicelleembeddedqdsandspiosdoesnotprovokeanacuteproinflammatoryresponseintheliver
AT bargheerdenise celltypespecificuptakeofpolymercoatedormicelleembeddedqdsandspiosdoesnotprovokeanacuteproinflammatoryresponseintheliver
AT giemsaartur celltypespecificuptakeofpolymercoatedormicelleembeddedqdsandspiosdoesnotprovokeanacuteproinflammatoryresponseintheliver
AT freundbarbara celltypespecificuptakeofpolymercoatedormicelleembeddedqdsandspiosdoesnotprovokeanacuteproinflammatoryresponseintheliver
AT schejaludger celltypespecificuptakeofpolymercoatedormicelleembeddedqdsandspiosdoesnotprovokeanacuteproinflammatoryresponseintheliver
AT waurischchristian celltypespecificuptakeofpolymercoatedormicelleembeddedqdsandspiosdoesnotprovokeanacuteproinflammatoryresponseintheliver
AT eychmulleralexander celltypespecificuptakeofpolymercoatedormicelleembeddedqdsandspiosdoesnotprovokeanacuteproinflammatoryresponseintheliver
AT reimerrudolph celltypespecificuptakeofpolymercoatedormicelleembeddedqdsandspiosdoesnotprovokeanacuteproinflammatoryresponseintheliver
AT wellerhorst celltypespecificuptakeofpolymercoatedormicelleembeddedqdsandspiosdoesnotprovokeanacuteproinflammatoryresponseintheliver
AT nielsenpeter celltypespecificuptakeofpolymercoatedormicelleembeddedqdsandspiosdoesnotprovokeanacuteproinflammatoryresponseintheliver
AT heerenjoerg celltypespecificuptakeofpolymercoatedormicelleembeddedqdsandspiosdoesnotprovokeanacuteproinflammatoryresponseintheliver