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Positive MRI Enhancement in THP-1 Cells with Gd2O3 Nanoparticles
Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
Linköping University, Department of Physics, Chemistry and Biology, Molecular Surface Physics and Nano Science. Linköping University, Faculty of Science & Engineering.
Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Physics, Chemistry and Biology, Physical Chemistry. Linköping University, Faculty of Science & Engineering.
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2008 (English)In: Contrast Media and Molecular Imaging, ISSN 1555-4309, Vol. 3, no 3, 106-111 p.Article in journal (Refereed) Published
Abstract [en]

There is a demand for more efficient and tissue-specific MRI contrast agents and recent developments involve the design of substances useful as molecular markers and magnetic tracers. In this study, nanoparticles of gadolinium oxide (Gd2O3) have been investigated for cell labeling and capacity to generate a positive contrast. THP-1, a monocytic cell line that is phagocytic, was used and results were compared with relaxivity of particles in cell culture medium (RPMI 1640). The results showed that Gd2O3-labeled cells have shorter T1 and T2 relaxation times compared with untreated cells. A prominent difference in signal intensity was observed, indicating that Gd2O3 nanoparticles can be used as a positive contrast agent for cell labeling. The r1 for cell samples was 4.1 and 3.6 s-1 mm-1 for cell culture medium. The r2 was 17.4 and 12.9 s-1 mm-1, respectively. For r1, there was no significant difference in relaxivity between particles in cells compared to particles in cell culture medium, (pr1 = 0.36), but r2 was significantly different for the two different series (pr2 = 0.02). Viability results indicate that THP-1 cells endure treatment with Gd2O3 nanoparticles for an extended period of time and it is therefore concluded that results in this study are based on viable cells.

Place, publisher, year, edition, pages
2008. Vol. 3, no 3, 106-111 p.
Keyword [en]
gadolinium oxide, nanoparticles, contrast agent, THP-1 cells, magnetic resonance imaging
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-12945DOI: 10.1002/cmmi.236ISI: 000257982000002OAI: oai:DiVA.org:liu-12945DiVA: diva2:17499
Available from: 2008-02-21 Created: 2008-02-21 Last updated: 2017-09-22Bibliographically approved
In thesis
1. MRI Contrast Enhancement using Gd2O3 Nanoparticles
Open this publication in new window or tab >>MRI Contrast Enhancement using Gd2O3 Nanoparticles
2008 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

There is an increasing interest for nanomaterials in biomedical applications and in this work, nanoparticles of gadolinium oxide (Gd2O3) have been investigated as a novel contrast agent for Magnetic Resonance Imaging (MRI). Relaxation properties have been studied in aqueous solutions as well as in cell culture medium and the nanoparticles have been explored as cell labeling agents. The fluorescent properties of the particles were used to visualize the internalization in cells and doped particles were also investigated as a multimodal agent that could work as a fluorescent marker for microscopy and as a contrast enhancer for MRI.

Results show that in aqueous solutions, there is a twofold increase in relaxivity for Gd2O3 compared to commercial agent Gd-DTPA. In cell culture medium as well as in cells, there is a clear T1 effect and a distinct increase in signal intensity in T1-mapped images. Fluorescent studies show that the Gd2O3 nanoparticles doped with 5% terbium have interesting fluorescent properties and that these particles could work as a multimodal contrast agent.

This study shows that Gd2O3 nanoparticles possess excellent relaxation properties that are retained in more biological environments. Gd2O3 particles are suitable as a T1 contrast agent, but seem also be adequate for T2 enhancement in for instance cell labeling experiments.

Place, publisher, year, edition, pages
Universitetsbibliotek, 2008. 116 p.
Series
Linköping Studies in Health Sciences. Thesis, ISSN 1100-6013 ; 85
Keyword
nanoparticles, gadolinium oxide, magnetic resonance imaging, contrast agent
National Category
Clinical Science
Identifiers
urn:nbn:se:liu:diva-11041 (URN)978-91-7393-966-9 (ISBN)
Presentation
2008-03-07, Conrad, Huvudblocket, plan 11, Campus US, Linköpings universitet, Linköping, 13:00 (English)
Supervisors
Available from: 2008-02-21 Created: 2008-02-21 Last updated: 2013-09-04
2. MRI Contrast Enhancement and Cell Labeling using Gd2O3 Nanoparticles
Open this publication in new window or tab >>MRI Contrast Enhancement and Cell Labeling using Gd2O3 Nanoparticles
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

There is an increasing interest for nanomaterials in bio-medical applications and in this work, nanoparticles of gadolinium oxide (Gd2O3 ) have been investigated as a novel contrast agent for magnetic resonance imaging (MRI). Relaxation properties have been studied in aqueous solutions as well as in cell culture medium and the nanoparticles have been explored as cell labeling agents. The fluorescent properties of the particles were used to visualize the internalization in cells and doped particles were investigated as a multimodal agent that could work as a fluorescent marker for microscopy and as a contrast enhancer for MRI. Fluorescent studies show that the Gd2O3 nanoparticles doped with 5% terbium have interesting fluorescent properties and that these particles could work as such multimodal contrast agent. Relaxivity measurements show that in aqueous solutions, there is a twofold increase in relaxivity for Gd2O3 compared to commercial agent Gd-DTPA. In cell culture medium as well as in cells, there is a clear T1 effect and an increase in signal intensity in T1-mapped images. The cellular uptake of Gd2O3 nanoparticles were increased with the use of transfection agent protamine sulfate. This work shows that Gd2O3 nanoparticles possess good relaxation properties that are retained in different biological environments. Gd2O3 particles are suitable as a T1 contrast agent, but seem also be adequate for T2 enhancement in forinstance cell labeling experiments.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2011. 73 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1230
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-68802 (URN)978-91-7393-215-8 (ISBN)
Public defence
2011-06-08, Wrannesalen, Universitetssjukhuset, CMIV, Campus US, Linköpings universitet, Linköping, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2011-06-07 Created: 2011-06-07 Last updated: 2013-09-05Bibliographically approved
3. Metal Oxide Nanoparticles for Contrast Enhancement in Magnetic Resonance Imaging: Synthesis, Functionalization and Characterization
Open this publication in new window or tab >>Metal Oxide Nanoparticles for Contrast Enhancement in Magnetic Resonance Imaging: Synthesis, Functionalization and Characterization
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis work focuses on the design and production of nanoparticle based contrast agents for signal enhancement in magnetic resonance imaging (MRI). Three different synthesis routes are explored, primarily to produce crystalline gadolinium oxide (Gd2O3) nanoparticles, and surface modification is done to obtain stable, dispersible, biocompatible probes inducing high proton relaxivities.

In Paper I and II we utilized the polyol synthesis method and nanoparticle purification was performed with dialysis. Active surface functionalization was achieved by an innermost layer of 3-mercaptopropyl trimetoxy silanes (MPTS) and an outer layer of bifunctional PEG. Surface capping was shown to greatly affect the water proton relaxation to a degree which is strongly dependent on the purification time. PEGylation also induced stabilizing effects and the ability to provide the nanoparticles with luminescent properties was proven by linking the fluorescent dye Rhodamine to the bifunctional PEG.

In Paper III the magnetic behavior of yttrium (Y) alloyed Gd2O3 nanoparticles was investigated as a function of Y concentration. This was done by performing magnetic measurements and by studying the signal line width in electron paramagnetic resonance spectroscopy for Gd2O3, Y2O3 and a series of (GdxY1-x)2O3 samples produced using the combustion synthesis. The results verified that the signal line width is dependent on the percent of yttrium dilution. This is considered as an indication of that yttrium dilution changes the electron spin relaxation time in Gd2O3.

Paper IV and V present a novel precipitation synthesis method for Gd2O3 nanoparticles. Acetate molecular groups were found to coordinate the nanoparticle surface increasing the water dispersability. The Gd2O3 nanoparticles induce a twice as high relaxivity per gadolinium atom, as compared to the commercially available contrast agent Magnevist. Incorporation of luminescent europium (Eu3+) ions into the Gd2O3 nanoparticles in combination with surface modification with a fluorescent branched carboxyl terminated TEG, produced dual probes with tunable luminescence, maintained relaxivity and thus a bright contrast in MRI.

In Paper VI, a new approach to accomplish a dual probe was investigated. Luminescent ZnO nanoparticles decorated with Gd ions bound in an organic matrix were evaluated for MR signal enhancement and ability to function as fluorescent probes. Interestingly, these nanoprobes did show an enhanced capability to both strengthen the MR signal and increase the fluorescent quantum yield, as compared to the pure oxides.

In Paper VII we investigate sub 5 nm crystalline manganese based nanoparticles produced by the precipitation synthesis used for Gd2O3 nanoparticles. Manganese oxide was chosen as another candidate for MRI contrast enhancement as it is expected to have a straight forward surface coupling chemistry. Characterization of the crystal structure and chemical composition indicated nanoparticles with a MnO core and presence of manganese species of higher valences at the nanoparticle surface. The MnO nanomaterial showed a superparamagnetic behavior and less capability to increase the MR signal as compared to Gd2O3.

Characterization of the nanoparticle crystal structure and size is, throughout the work, performed by means of transmission electron microscopy, X-ray diffraction and dynamic light scattering. The chemical composition is studied with X-ray photoelectron spectroscopy, infrared spectroscopy and near edge X-ray absorption fine structure spectroscopy and the fluorescence characteristics are evaluated with fluorescence spectroscopy. In addition, theoretical models and calculated IR spectroscopy and near edge X-ray absorption fine structure spectroscopy data have been used for evaluation of experimental results.

To conclude, the aim of this work is the design, production and characterization of ultrasmall rare earth based nanoparticles for signal enhancement in biomedical imaging. Surface modification clearly increases the colloidal stability and biocompatibility of the nanoparticles. Compared to the agents in clinical use today, these nanoprobes have a higher capability to enhance the MR-signal, and they will in the near future be equipped with tags for specific targeting.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2013. 82 p.
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1541
National Category
Natural Sciences
Identifiers
urn:nbn:se:liu:diva-98693 (URN)10.3384/diss.diva-98693 (DOI)978-91-7519-522-3 (ISBN)
Public defence
2013-11-15, Brillouin, Fysikhuset, Campus Valla, Linköpings universitet, Linköping, 10:15 (Swedish)
Opponent
Supervisors
Available from: 2013-10-11 Created: 2013-10-11 Last updated: 2015-06-03Bibliographically approved

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Klasson, AnnaAhrén, MariaHellqvist, EvaSöderlind, FredrikRosén, AndersKäll, Per-OlovUvdal, KajsaEngström, Maria

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