Endre søk
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Effects of gadolinium oxide nanoparticles on the oxidative burst from human neutrophil granulocytes
Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär ytfysik och nanovetenskap. Linköpings universitet, Tekniska fakulteten.
Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär ytfysik och nanovetenskap. Linköpings universitet, Tekniska högskolan.
Linköpings universitet, Institutionen för fysik, kemi och biologi, Molekylär ytfysik och nanovetenskap. Linköpings universitet, Tekniska fakulteten.
University of Örebro, Sweden .
Vise andre og tillknytning
2012 (engelsk)Inngår i: Nanotechnology, ISSN 0957-4484, E-ISSN 1361-6528, Vol. 23, nr 27, s. 275101-Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

We have previously shown that gadolinium oxide (Gd2O3) nanoparticles are promising candidates to be used as contrast agents in magnetic resonance (MR) imaging applications. In this study, these nanoparticles were investigated in a cellular system, as possible probes for visualization and targeting intended for bioimaging applications. We evaluated the impact of the presence of Gd2O3 nanoparticles on the production of reactive oxygen species (ROS) from human neutrophils, by means of luminol-dependent chemiluminescence. Three sets of Gd2O3 nanoparticles were studied, i.e. as synthesized, dialyzed and both PEG-functionalized and dialyzed Gd2O3 nanoparticles. In addition, neutrophil morphology was evaluated by fluorescent staining of the actin cytoskeleton and fluorescence microscopy. We show that surface modification of these nanoparticles with polyethylene glycol (PEG) is essential in order to increase their biocompatibility. We observed that the as synthesized nanoparticles markedly decreased the ROS production from neutrophils challenged with prey (opsonized yeast particles) compared to controls without nanoparticles. After functionalization and dialysis, more moderate inhibitory effects were observed at a corresponding concentration of gadolinium. At lower gadolinium concentration the response was similar to that of the control cells. We suggest that the diethylene glycol (DEG) present in the as synthesized nanoparticle preparation is responsible for the inhibitory effects on the neutrophil oxidative burst. Indeed, in the present study we also show that even a low concentration of DEG, 0.3%, severely inhibits neutrophil function. In summary, the low cellular response upon PEG-functionalized Gd2O3 nanoparticle exposure indicates that these nanoparticles are promising candidates for MR-imaging purposes.

sted, utgiver, år, opplag, sider
Institute of Physics , 2012. Vol. 23, nr 27, s. 275101-
HSV kategori
Identifikatorer
URN: urn:nbn:se:liu:diva-79667DOI: 10.1088/0957-4484/23/27/275101ISI: 000305802000001OAI: oai:DiVA.org:liu-79667DiVA, id: diva2:544294
Tilgjengelig fra: 2012-08-14 Laget: 2012-08-13 Sist oppdatert: 2018-11-12
Inngår i avhandling
1. Investigation of nanoparticle-cell interactions for development of next generation of biocompatible MRI contrast agents
Åpne denne publikasjonen i ny fane eller vindu >>Investigation of nanoparticle-cell interactions for development of next generation of biocompatible MRI contrast agents
2018 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

Progress in synthesis technologies and advances in fundamental understanding of materials with low dimensionality has led to the birth of a new scientific field, nanoscience, and to strong expectations of multiple applications of nanomaterials. The physical properties of small particles are unique, bridging the gap between atoms and molecules, on one side, and bulk materials on the other side. The work presented in this thesis investigates the potential of using magnetic nanoparticles as the next generation of contrast agents for biomedical imaging. The focus is on gadolinium-based nanoparticles and cellular activity including the uptake, morphology and production of reactive oxygen species.

Gd ion complexes, like Gd chelates, are used today in the clinic, world-wide. However, there is a need for novel agents, with improved contrast capabilities and increased biocompatibility. One avenue in their design is based on crystalline nanoparticles. It allows to reduce the total number of Gd ions needed for an examination. This can be done by nanotechnology, which allows one to improve and fine tune the physico- chemical properties on the nanomaterial in use, and to increase the number of Gd atoms at a specific site that interact with protons and thereby locally increase the signal. In the present work, synthesis, purification and surface modification of crystalline Gd2O3-based nanoparticles have been performed. The nanoparticles are selected on the basis of their physical properties, that is they show enhanced magnetic properties and therefore may be of high potential interest for applications as contrast agents.

The main synthesis method of Gd2O3 nanoparticles in this work was the modified “polyol” route, followed by purification of as-synthesized DEG-Gd2O3 nanoparticles suspensions. In most cases the purification step involved dialysis of the nanoparticle samples. In this thesis, organosilane were chosen as an exchange agent for further functionalization. Moreover, several paths have been explored for modification of the nanoparticles, including Tb3+ doping and capping with sorbitol.

Biocompatibility of the newly designed nanoparticles is a prerequisite for their use in medical applications. Its evaluation is a complex process involving a wide range of biological phenomena. A promising path adopted in this work is to study of nanoparticle interactions with isolated blood cells. In this way one could screen nanomaterial prior to animal studies.

The primary cell type considered in the thesis are polymorphonuclear neutrophils (PMN) which represent a type of the cells of human blood belonging to the granulocyte family of leukocytes. PMNs act as the first defense of the immune system against invading pathogens, which makes them valuable for studies of biocompatibility of newly synthesized nanoparticles. In addition, an immortalized murine alveolar macrophage cell line (MH-S), THP-1 cell line, and Ba/F3 murine bone marrow-derived cell line were considered to investigate the optimization of the cell uptake and to examine the potential of new intracellular contrast agent for magnetic resonance imaging.

In paper I, the nanoparticles were investigated in a cellular system, as potential probes for visualization and targeting intended for bioimaging applications. The production of reactive oxygen species (ROS) by means of luminol-dependent chemiluminescence from human neutrophils was studied in presence of Gd2O3 nanoparticles. In paper II, a new design of functionalized ultra-small rare earth-based nanoparticles was reported. The synthesis was done using polyol method followed by PEGylation, and dialysis. Supersmall gadolinium oxide (DEG-Gd2O3) nanoparticles, in the range of 3-5 nm were obtained and carefully characterized. Neutrophil activation after exposure to this nanomaterial was studied by means of fluorescence microscopy. In paper III, cell labeling with Gd2O3 nanoparticles in hematopoietic cells was monitored by magnetic resonance imaging (MRI). In paper IV, ultra-small gadolinium oxide nanoparticles doped with terbium ions were synthesized as a potentially bifunctional material with both fluorescent and magnetic contrast agent properties. Paramagnetic behavior was studied. MRI contrast enhancement was received, and the luminescent/ fluorescent property of the particles was attributable to the Tb3+ ion located on the crystal lattice of the Gd2O3 host. Fluorescent labeling of living cells was obtained. In manuscript V, neutrophil granulocytes were investigated with rapid cell signaling communicative processes in time frame of minutes, and their response to cerium-oxide based nanoparticles were monitored using capacitive sensors based on Lab-on-a-chip technology. This showed the potential of label free method used to measure oxidative stress of neutrophil granulocytes. In manuscript VI, investigations of cell-(DEGGd2O3) nanoparticle interactions were carried out. Plain (DEG-Gd2O3) nanoparticles, (DEG-Gd2O3) nanoparticles in presence of sorbitol and (DEG-Gd2O3) nanoparticles capped with sorbitol were studied. Relaxation studies and measurements of the reactive oxygen species production by neutrophils were based on chemiluminescence. Cell morphology was evaluated as a parameter of the nanoparticle induced inflammatory response by means of the fluorescence microscopy.

The thesis demonstrates high potential of novel Gd2O3-based nanoparticles for development of the next generation contrast agents, that is to find biocompatible compounds with high relaxivity that can be detected at lower doses, and in the future enable targeting to provide great local contrast.

sted, utgiver, år, opplag, sider
Linköping: Linköping University Electronic Press, 2018. s. 78
Serie
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1961
HSV kategori
Identifikatorer
urn:nbn:se:liu:diva-152347 (URN)9789176851906 (ISBN)
Disputas
2018-11-21, Planck, Fysikhuset, Campus Valla, Linköping, 10:15 (engelsk)
Opponent
Veileder
Tilgjengelig fra: 2018-10-29 Laget: 2018-10-29 Sist oppdatert: 2018-10-29bibliografisk kontrollert

Open Access i DiVA

Fulltekst mangler i DiVA

Andre lenker

Forlagets fulltekst

Søk i DiVA

Av forfatter/redaktør
Abrikossova, NataliaSkoglund, CarolineAhrén, MariaUvdal, Kajsa
Av organisasjonen
I samme tidsskrift
Nanotechnology

Søk utenfor DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric

doi
urn-nbn
Totalt: 593 treff
RefereraExporteraLink to record
Permanent link

Direct link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf