| 1. |
- Abrikossova, Natalia, et al.
(författare)
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Effects of gadolinium oxide nanoparticles on the oxidative burst from human neutrophil granulocytes
- 2012
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Ingår i: Nanotechnology. - Bristol, United Kingdom : IOP Publishing Ltd.. - 0957-4484 .- 1361-6528. ; 23:27
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Abrikossova, Natalia, 1965-
(författare)
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Investigation of nanoparticle-cell interactions for development of next generation of biocompatible MRI contrast agents
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 3. |
- Ahrén, Maria, et al.
(författare)
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A simple polyol-free synthesis route to Gd 2O 3 nanoparticles for MRI applications : An experimental and theoretical study
- 2012
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Ingår i: Journal of nanoparticle research. - : Springer. - 1388-0764 .- 1572-896X. ; 14:8
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Tidskriftsartikel (refereegranskat)abstract
- Chelated gadolinium ions, e.g., Gd-DTPA, are today used clinically as contrast agents for magnetic resonance imaging (MRI). An attractive alternative contrast agent is composed of gadolinium oxide nanoparticles as they have shown to provide enhanced contrast and, in principle, more straightforward molecular capping possibilities. In this study, we report a new, simple, and polyol-free way of synthesizing 4-5-nm-sized Gd 2O 3 nanoparticles at room temperature, with high stability and water solubility. The nanoparticles induce high-proton relaxivity compared to Gd-DTPA showing r 1 and r 2 values almost as high as those for free Gd 3+ ions in water. The Gd 2O 3 nanoparticles are capped with acetate and carbonate groups, as shown with infrared spectroscopy, near-edge X-ray absorption spectroscopy, X-ray photoelectron spectroscopy and combined thermogravimetric and mass spectroscopy analysis. Interpretation of infrared spectroscopy data is corroborated by extensive quantum chemical calculations. This nanomaterial is easily prepared and has promising properties to function as a core in a future contrast agent for MRI.
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| 4. |
- Ahrén, Maria, 1979-
(författare)
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Metal Oxide Nanoparticles for Contrast Enhancement in Magnetic Resonance Imaging : Synthesis, Functionalization and Characterization
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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| 5. |
- Ahrén, Maria, et al.
(författare)
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One-step synthesis of sub 5 nm sized manganese oxide based nanoparticles
- 2013
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Sub 5 nm sized manganese oxide nanoparticles; MnOx (1 ≤ x ≤ 2), were synthesized via a short time room temperature synthesis route. The nanoparticles are crystalline, spherically shaped and in the size range of 2-4 nm as shown by transmission electron microscopy studies. Selected area electron diffraction patterns were collected and their appearance indicated that the nanoparticle cores are composed of MnO. Also, co-existence of the (II) and (III) oxidation states at the nanoparticle surface was verified by results achieved from infrared spectroscopy and X-ray photoelectron spectroscopy. These measurements also supported presence of a minor amount of acetate groups as well as a negligible fraction of carbonate groups at the nanoparticle surfaces. The interpretation of the IR spectra was confirmed by quantum chemical calculations using the high spin manganese nanoparticle Mn12O12(OAc)16(H2O)4, as a model system for the MnOx nanoparticle surface. Bulk MnO and Mn2O3 are known to be antiferromagnetic. The magnetic properties are however somewhat dependent of the crystallite size and changes when scaling down to the nanoregion. The MnOx (1 ≤ x ≤ 2) nanoparticles investigated in this work show a superparamagnetic behavior with a blocking temperature of approximately 12 K proven by means of SQUID measurements. The relaxivities of the nanoparticles and the Mn(OAc)2 precursors were studied with a bench top NMR analyzer verifying nanoparticle r1 and r2 of 0.5 and 6 mMs-1 respectively. The r1 relaxivity is lower than what is earlier reported for Gd based contrast agent, but improvements are expected by further surface modification, due to increased rotational time and higher water dispersability.
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| 6. |
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| 7. |
- Ahrén, Maria, et al.
(författare)
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Synthesis and Characterization of PEGylated Gd2O3 Nanoparticles for MRI Contrast Enhancement
- 2010
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 26:8, s. 5753-5762
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Tidskriftsartikel (refereegranskat)abstract
- Recently, much attention has been given to the development of biofunctionalized nanoparticles with magnetic properties for novel biomedical imaging. Guided, smart, targeting nanoparticulate magnetic resonance imaging (MRI) contrast agents inducing high MRI signal will be valuable tools for future tissue specific imaging and investigation of molecular and cellular events. In this study. We report a new design of functionalized ultrasmall rare earth based nanoparticles to be used as a positive contrast agent in NI RI. The relaxivity is compared to commercially available Gd based chelates. The synthesis, PEGylation, and dialysis of small (3-5 nm) gadolinium oxide (DEG-Gd2O3) nanoparticles are presented. The chemical and physical properties of the nanomaterial were investigated with Fourier transform infrared spectroscopy. X-ray photoelectron spectroscopy, transmission electron microscopy, and dynamic light scattering. Neutrophil activation after exposure to this nanomaterial was studied by means of fluorescence microscopy. The proton relaxation times as a function of dialysis time and functionalization were measured at 1.5 T. A capping procedure introducing stabilizing properties was designed and verified, and the dialysis effects were evaluated. A higher proton relaxivity was obtained for as-synthesized diethylene glycol (DEG)-Gd2O3 nanoparticles compared to commercial Gd-DTPA. A slight decrease of the relaxivity for as-synthesized DEG-Gd2O3 nanoparticles as a function of dialysis time was observed. The results for functionalized nanoparticles showed a considerable relaxivity increase for particles dialyzed extensively with r(1) and r(2) values approximately 4 times the corresponding values for Gd-DTPA. The microscopy study showed that PEGylated nanoparticles do not activate neutrophils in contrast to uncapped Gd2O3. Finally, the nanoparticles are equipped with Rhodamine to show that our PEGylated nanoparticles are available for further coupling chemistry, and thus prepared for targeting purposes. The long term goal is to design a powerful, directed contrast agent for MRI examinations with specific targeting possibilities and with properties inducing local contrast, that is. an extremely high MR signal at the cellular and molecular level.
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| 8. |
- Alfredsson, Ylvi, 1973-
(författare)
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Electronic and Structural Properties of Thin Films of Phthalocyanines and Titanium Dioxide
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is based on experimental studies in chemical physics. Titanium dioxide (TiO2) and phthalocyanine’s (Pc’s), interesting in many future perspectives, have been deposited as thin films and studied as follows. Information has been obtained on e.g. molecular orientation, crystal structure, depth profile of the chemical composition, electrochemical properties and electronic structure. This has been achieved by means of a combination of techniques: X-ray photoelectron spectroscopy (XPS), near edge x-ray absorption fine structure (NEXAFS), density functional theory calculations (DFT), UV-visible absorption spectroscopy (UVVIS) and cyclic voltammetry (CV).Metal-free phthalcyanine (H2Pc) has been shown to form films with different crystal structure and molecular orientation depending on deposition method, evaporation/sublimation or powder deposition, on commercial conducting glass (fluorine doped tin oxide, FTO), which is used e.g. in solar cells and organic light emitting devices (OLEDs). The unoccupied molecular orbitals are divided in x, y and z space coordinates of the molecule and also divided in inequivalent nitrogen components.The electronic structure is also studied for a sublimated titanyl phthalocyanine (TiOPc) film and related to the metal-free phthalocyanine. The ligand field around the titanium atom in TiOPc is compared with that of TiO2 to delineate the unoccupied levels recorded by means of x-ray absorption spectroscopy.Nanostructured TiO2 films were manufactured by screen printing/doctor blading on FTO. Such films were additionally covered with lutetium diphthalocyanine (LuPc2) by means of surface assembly from solution. LuPc2-, LuPc2+ and LuPc2H were identified and the stability of the electrochromic reactions in this system was monitored.Chemical vapor deposition (CVD) has been used to grow nanometer sized anatase TiO2 crystals on pre-oxidized Si (111) without formation of interfacial carbon and with an interface layer of the size of 15- 25Å. The interface layer was found to be amorphous TiSixOy with graded stoichiometry.
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| 9. |
- Andersson, Viktor, et al.
(författare)
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Preparation of amyloidlike fibrils containing magnetic iron oxide nanoparticles: Effect of protein aggregation on proton relaxivity
- 2012
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier. - 0006-291X .- 1090-2104. ; 419:4, s. 682-686
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Tidskriftsartikel (refereegranskat)abstract
- A method to prepare amyloid-like fibrils functionalized with magnetic nanoparticles has been developed. The amyloid-like fibrils are prepared in a two step procedure, where insulin and magnetic nanoparticles are mixed simply by grinding in the solid state, resulting in a water soluble hybrid material. When the hybrid material is heated in aqueous acid, the insulin/nanoparticle hybrid material self assembles to form amyloid-like fibrils incorporating the magnetic nanoparticles. This results in magnetically labeled amyloid-like fibrils which has been characterized by Transmission Electron Microscopy (TEM) and electron tomography. The influence of the aggregation process on proton relaxivity is investigated. The prepared materials have potential uses in a range of bio-imaging applications.
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| 10. |
- Assenhöj, Maria, et al.
(författare)
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Protein interaction, monocyte toxicity and immunogenic properties of cerium oxide crystals with 5% or 14% gadolinium, cobalt oxide and iron oxide nanoparticles–an interdisciplinary approach
- 2021
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Ingår i: Nanotoxicology. - : Taylor and Francis Ltd.. - 1743-5390 .- 1743-5404. ; 15:8, s. 1035-1038
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Tidskriftsartikel (refereegranskat)abstract
- Metal oxide nanoparticles are widely used in both consumer products and medical applications, but the knowledge regarding exposure-related health effects is limited. However, it is challenging to investigate nanoparticle interaction processes with biological systems. The overall aim of this project was to improve the possibility to predict exposure-related health effects of metal oxide nanoparticles through interdisciplinary collaboration by combining workflows from the pharmaceutical industry, nanomaterial sciences, and occupational medicine. Specific aims were to investigate nanoparticle-protein interactions and possible adverse immune reactions. Four different metal oxide nanoparticles; CeOx nanocrystals with 5% or 14% Gd, Co3O4, and Fe2O3, were characterized by dynamic light scattering and high-resolution transmission electron microscopy. Nanoparticle-binding proteins were identified and screened for HLA-binding peptides in silico. Monocyte interaction with nanoparticle–protein complexes was assessed in vitro. Herein, for the first time, immunogenic properties of nanoparticle-binding proteins have been characterized. The present study indicates that especially Co3O4-protein complexes can induce both ‘danger signals’, verified by the production of inflammatory cytokines and simultaneously bind autologous proteins, which can be presented as immunogenic epitopes by MHC class II. The clinical relevance of these findings should be further evaluated to investigate the role of metal oxide nanoparticles in the development of autoimmune disease. The general workflow identified experimental difficulties, such as nanoparticle aggregate formation and a lack of protein-free buffers suitable for particle characterization, protein analyses, as well as for cell studies. This confirms the importance of future interdisciplinary collaborations. © 2021 The Author(s).
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| 11. |
- Balian, Alien, 1988-
(författare)
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Nuclease Activity as a Biomarker in Cancer Detection
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Nucleases are a group of enzymes that cleave the phosphodiester bonds in nucleic acids. As such, nucleases act as biological scissors that exhibit a plethora of fundamental roles, in prokaryotes and eukaryotes, dependent or non-dependent on their catalytic capability. Thus, differential status of nucleases between healthy and disease conditions might not be surprising, and can be deployed in disease detection. Specifically, there is growing body of research demonstrating the potential of nucleases as diagnostic biomarkers in several types of cancer. Biomarkers for early diagnosis are an immense need in the diagnostic landscape of cancer. In this sense, nucleases are promising biomolecules, and they possess a unique feature of catalytic activity that could be deployed for diagnosis and future therapeutic strategies. In this thesis we aim to demonstrate the use of nucleases as biomarkers associated to cancer, and the capability of oligonucleotide substrates for targeting a specific nuclease. The thesis work begins with comprehensive review of nucleases as promising biomarkers in cancer diagnosis (paper I). Then, we provide a methodological study in paper II, in which we propose a flexible approach for detection of disease associated nuclease activity using oligonucleotides as substrates. The probes utilized here are flanked with fluorophore at the 5’-end and a quencher at the 3’-end. Upon cleavage by nucleases, the fluorescent signal is increased in a proportional fashion to nuclease activity. This platform is suitable to implement in detection of any disease in which nuclease activity is altered. We have applied this method in paper III, by using 75 probes as substrates to screen breast cancer cells, along with controls, for nuclease activity. We have identified a probe (DNA PolyAT) that discriminates between BT-474 breast cancer cells and healthy cells based on nuclease activity profile associated with cell membrane. Next, we screened tissue samples from breast tumors for nuclease activity, and we have identified a set of probes with the capability to discriminate breast tumor and healthy tissues in 89% of the cases (paper IV). To achieve a step forward towards non-invasive diagnosis, we have developed an activatable magnetic resonance imaging (MRI)-probe (paper V). The MRI-probe is oligonucleotide-based that works like a contrast agent, and it is activated only in presence of a specific nuclease. MRI-probes provide advantages over fluorescent probes, such as high spatial resolution and unlimited tissue penetration. In conclusion, our findings suggest the utility of nuclease activity as a biomarker in cancer detection. Moreover, we demonstrate the applicability of nuclease activity-based approaches in imaging modalities, such as MRI. Our future aim is to translate our findings into non-invasive detection of breast cancer by utilizing breast cancer activatable MRI-probes.
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| 12. |
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| 13. |
- Björefors, Fredrik, et al.
(författare)
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Electrochemical impedance spectroscopy for investigations on ion permeation in ?-functionalized self-assembled monolayers
- 2007
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 79:21, s. 8391-8398
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Tidskriftsartikel (refereegranskat)abstract
- Electrochemical impedance spectroscopy was employed to explore the possibility of relating the permeation of electrolyte ions in ?-functionalized self-assembled monolayers to structural or polarity changes induced by interaction with metal ions. The monolayers were based on alkanethiols modified with a phosphorylated tyrosine analogue, which from previous work are known to drastically change their organization on gold surfaces upon interaction with aluminum and magnesium ions. The ion permeation was evaluated by using relatively low excitation frequencies, 1000 to 2 Hz, and quantified by an extra resistive component in the equivalent circuit (R SAM). The extent of ion permeation influenced by the dc potential, the electrolyte concentration, the functional group, and the thiol length were also investigated. It was, for example, found that RSAM decreased ~20% when the thiol organization collapsed and that RSAM increased ~4-5 times when the electrolyte concentration was decreased by 1 order of magnitude. Interesting observations were also made regarding the potential dependence of RSAM and the double layer capacitance. The evaluation of the ion permeation can be used to indirectly detect whether the organization of a SAM is influenced by, for example, electric fields or chemical and biological interactions. This analysis can be performed without addition of redox species, but is on the other hand complicated by the fact that other factors also influence the presence of ions within the monolayer. In addition, a second parallel RC process was obtained in some of the impedance spectra when using even lower frequencies, and its resistive component revealed different results compared to RSAM. Such data may be useful for the understanding of complex double layer phenomena at modified electrodes. © 2007 American Chemical Society.
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| 14. |
- Borgh, Annika, et al.
(författare)
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A new route to the formation of biomimetic phosphate assemblies on gold : Synthesis and characterization
- 2006
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 1095-7103 .- 0021-9797. ; 295:1, s. 41-49
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Tidskriftsartikel (refereegranskat)abstract
- A biomimetic model system based on long-chain alkanethiols tailored with serine, threonine and tyrosine side-chain groups is created as a platform for the study of phosphorylated amino acids. The phosphorylated analogues are synthesized with protective tert-butyl groups that after assembly on thin polycrystalline gold films are removed in an acidic deprotection solution to form the corresponding phosphate self-assembled monolayers (SAMs). The SAMs are thoroughly characterized with null ellipsometry, contact angle goniometry, infrared reflection–absorption spectroscopy and X-ray photoelectron spectroscopy. The assembly and the subsequent deprotection process are optimized with respect to molecular orientation and chain conformation by varying the incubation time and the exposure time to the deprotection solution. The high quality of the generated SAMs suggests that the present assembly/deprotection approach is an attractive alternative when traditional synthetic routes become demanding because of solubility problems.
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| 15. |
- Bunnfors, Kalle, 1989-
(författare)
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Imaging and Spectroscopic Mapping of Blood Cell Activity : Nanoparticles and Neutrophil Extracellular Traps
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Imaging and visualization of cell activity when exposed to nanomaterial are of main importance, when investigating biological response to a wide range of biomaterials from medical implants to smart nanoprobes. The ability to provide molecular and chemical information with spatial resolution in the region of sub-µm leads to increased insight and understanding of these biological challenges. Interdisciplinary collaborative effort may contribute and help solving urgent matters related to the challenges that we globally share. It is necessary to develop powerful tools such as analytical imaging techniques for addressing these urgent issues. This will increase our knowledge from the visualization on the cellular and subcellular level and help designing sustainable, personalized medical nanoprobes. In this thesis, the focus is to investigate the possibilities using the fluorescence microscopy, combined with surface analytical techniques delivering element specific information. Neutrophils are the most abundant immune cell in our bodies. They scavenge the body for threats and are usually among the first ones to find intruders and start the inflammation process. They have several ways of handling a threat, the main three being degranulation, phagocytosis, and neutrophil extracellular traps (NETs). In short, degranulation where granules are released into the extracellular matrix, phagocytosis is the process when for example the bacteria in engulfed by the neutrophil and neutralized. The NETs are when the neutrophil decondense their DNA and throw it out as a net to physically trap the invader and together with reactive oxygen species, proteases, and other antimicrobial molecules. It has been observed that nanoparticles (NP) can trigger NETs and there have been some comparisons between different parameters such as size, geometry, and functionalization. In this thesis we have explored how to measure neutrophil activity by a novel label free and noninvasive method (Paper 1). The NanoEsca, a combined XPS and PEEM instrument, is used to chemically map the neutrophils and NETs. We could clearly observe the NETs in PEEM and XPS mode. Quantum Dots (QDots, CdSe based) was used to trigger NETs. We track down the Quantum Dots with the element specific mapping. In the next paper we further explored how to extract new information with this advanced instrument that is traditionally is used for material- and surface science, and just recently deliver results in imaging and visualization within life sciences. Ultrathin slices of neutrophils where made special focus was given to the research work developing strategies to obtain and extract additional information from inside the neutrophils. These are pilot studies and show great potential to get chemical information in a label free way and is a good complement to fluorescence, SEM and TEM. We then made an in-depth investigation on the mechanisms how nanoparticles interact with neutrophils, with special focus on processes triggering NETs formation. Using QDots as a model system we could show that the NETs release is strongly dependent on the uptake of the nanoparticles. We used fluorescence and TEM to investigate where the QDots uptake and to identify the pattern where they finally end up. We clearly observed them inside vesicles in the inner part of the cell and even within the NETs structure giving proof that the uptake of QDots play an important role of the NETs formation. In the last paper we expanded the study and exposed the cells to Iron Oxide NPs (FeNP) Here we developed a strategy how to alternate the magnetic field control the direction of the NETs. We could manipulate live NETs with a magnetic field and made observations that parts of the NETs are static and some clearly mobile, still with an internal memory to find its initial structure just after release. TEM studies revealed that, like the QDots, the FeNP end up inside the NETs. In conclusion in this thesis work, detailed processes are explored on neutrophils and their NETs formation with new unconventional methods and how neutrophils and nanoparticles interact with respect to NETs.
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| 16. |
- Bunnfors, Kalle, et al.
(författare)
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Nanoparticle activated neutrophils-on-a-chip : A label-free capacitive sensor to monitor cells at work
- 2020
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Ingår i: Sensors and actuators. B, Chemical. - : Elsevier. - 0925-4005 .- 1873-3077. ; 313
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Tidskriftsartikel (refereegranskat)abstract
- Neutrophil granulocytes are the most abundant white blood cells in mammals and vital components of the immune system. They are involved in the early phase of inflammation and in generation of reactive oxygen species. These rapid cell-signaling communicative processes are performed in the time frame of minutes. In this work, the activity and the response of neutrophil granulocytes are monitored when triggered by cerium-oxide based nanoparticles, using capacitive sensors based on Lab-on-a-chip technology. The chip is designed to monitor activation processes of cells during nanoparticle exposure, which is for the first time recorded on-line as alteration of the capacitance. The complementary metal oxide semiconductor engineering chip design is combined with low temperature co-fired ceramic, LTCC, packaging technology. The method is label free and gently measures cells on top of an insulating surface in a weak electromagnetic field, as compared to commonly used four-point probes and impedance spectroscopy electric measurements where electrodes are in direct contact with the cells. In summary, this label free method is used to measure oxidative stress of neutrophil granulocytes in real time, minute by minute and visualize the difference in moderate and high cellular workload during exposure of external triggers. It clearly shows the capability of this method to detect cell response during exposure of external triggers. In this way, an informationally dense non-invasive method is obtained, to monitor cells at work.
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| 17. |
- Chen, Zhiwen, et al.
(författare)
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Integrated Design of Hierarchical CoSnO3@NC@MnO@NC Nanobox as Anode Material for Enhanced Lithium Storage Performance
- 2020
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Ingår i: ACS Applied Materials and Interfaces. - : AMER CHEMICAL SOC. - 1944-8244 .- 1944-8252. ; 12:17, s. 19768-19777
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Tidskriftsartikel (refereegranskat)abstract
- Transition-metal oxides (TMOs) are potential candidates for anode materials of lithium-ion batteries (LIBs) due to their high theoretical capacity (similar to 1000 mA h/g) and enhanced safety from suppressing the formation of lithium dendrites. However, the poor electron conductivity and the large volume expansion during lithiation/delithiation processes are still the main hurdles for the practical usage of TMOs as anode materials. In this work, the CoSnO3@NC@ MnO@NC hierarchical nanobox (CNMN) is then proposed and fabricated to solve those issues. The as-prepared nanobox contains hollow cubic CoSnO3 as a core and dual N-doped carbon-"sandwiched" MnO particles as a shell. As anode materials of LIBs, the hollow and carbon interlayer structures effectively accommodate the volume expansion while dual active TMOs of CoSnO3 and Notably, the dual-layer structure of N-doped carbons plays a critical functional role MnO efficiently increase the specific capacity. in the incorporated composites, where the inner layer serves as a reaction substrate and a spatial barrier and the outer layer offers electron conductivity, enabling more effective involvement of active anode materials in lithium storage, as well as maintaining their high activity during lithium cycling. Subsequently, the as-prepared CNMN exhibits a high specific capacity of 1195 mA h/g after the 200th cycle at 0.1C and an excellent stable reversible capacity of about 876 mA h/g after the 300th cycle at 0.5C with only 0.07 mA h/g fade per cycle after 300 cycles. Even after a 250 times fast charging/discharging cycle both at SC, it still retains a reversible capacity of 422.6 mA h/g. We ascribe the enhanced lithium storage performances to the novel hierarchical architectures achieved from the rational design.
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| 18. |
- Dahlstedt, Emma, et al.
(författare)
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Synthesis of tetrathiafulvalenes suitable for self-assembly applications
- 2004
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Ingår i: Journal of Materials Chemistry. - : Royal Society of Chemistry (RSC). - 0959-9428 .- 1364-5501. ; 14:1, s. 81-85
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Tidskriftsartikel (refereegranskat)abstract
- A series of new tetrathiafulvalenes, with double alkylthiol or alkyldisulfide substitution, have been prepared with a synthetic procedure that allows variation of different substituents. The target compounds 6a-e and 15e-i are sparsely soluble in organic solvents, but TTFs 6d and 15g gave a relatively dense packed monolayer upon exposure to gold surfaces.
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| 19. |
- Ding, Yang, et al.
(författare)
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Artificial intelligence-assisted point-of-care testing system for ultrafast and quantitative detection of drug-resistant bacteria
- 2023
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Ingår i: SMARTMAT. - : WILEY. - 2766-8525.
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Tidskriftsartikel (refereegranskat)abstract
- As one of the major causes of antimicrobial resistance, beta-lactamase develops rapidly among bacteria. Detection of beta-lactamase in an efficient and low-cost point-of-care testing (POCT) way is urgently needed. However, due to the volatile environmental factors, the quantitative measurement of current POCT is often inaccurate. Herein, we demonstrate an artificial intelligence (AI)-assisted mobile health system that consists of a paper-based beta-lactamase fluorogenic probe analytical device and a smartphone-based AI cloud. An ultrafast broad-spectrum fluorogenic probe (B1) that could respond to beta-lactamase within 20 s was first synthesized, and the detection limit was determined to be 0.13 nmol/L. Meanwhile, a three-dimensional microfluidic paper-based analytical device was fabricated for integration of B1. Also, a smartphone-based AI cloud was developed to correct errors automatically and output results intelligently. This smart system could calibrate the temperature and pH in the beta-lactamase level detection in complex samples and mice infected with various bacteria, which shows the problem-solving ability in interdisciplinary research, and demonstrates potential clinical benefits.
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| 20. |
- Engström, Maria, et al.
(författare)
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High Proton Relaxivity for Gadolinium Oxide Nanoparticles
- 2006
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Ingår i: Magnetic Resonance Materials in Physics, Biology and Medicine. - : Springer Science and Business Media LLC. - 0968-5243 .- 1352-8661. ; 19:4, s. 180-186
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Nanosized materials of gadolinium oxide can provide high-contrast enhancement in magnetic resonance imaging (MRI). The objective of the present study was to investigate proton relaxation enhancement by ultrasmall (5 to 10 nm) Gd2O3 nanocrystals.Materials and methods: Gd2O3 nanocrystals were synthesized by a colloidal method and capped with diethylene glycol (DEG). The oxidation state of Gd2O3 was confirmed by X-ray photoelectron spectroscopy. Proton relaxation times were measured with a 1.5-T MRI scanner. The measurements were performed in aqueous solutions and cell culture medium (RPMI).Results: Results showed a considerable relaxivity increase for the Gd2O3–DEG particles compared to Gd-DTPA. Both T 1 and T 2 relaxivities in the presence of Gd2O3–DEG particles were approximately twice the corresponding values for Gd–DTPA in aqueous solution and even larger in RPMI. Higher signal intensity at low concentrations was predicted for the nanoparticle solutions, using experimental data to simulate a T1-weighted spin echo sequence.Conclusion: The study indicates the possibility of obtaining at least doubled relaxivity compared to Gd–DTPA using Gd2O3–DEG nanocrystals as contrast agent. The high T 1 relaxation rate at low concentrations of Gd2O3 nanoparticles is very promising for future studies of contrast agents based on gadolinium-containing nanocrystals.
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| 21. |
- Eriksson, Jens, et al.
(författare)
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Modified Epitaxial Graphene on SiC for Extremely Sensitive andSelective Gas Sensors
- 2016
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Ingår i: Materials Science Forum. - : Trans Tech Publications Inc.. - 0255-5476 .- 1662-9752. ; 858, s. 1145-1148
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Tidskriftsartikel (refereegranskat)abstract
- Two-dimensional materials offer a unique platform for sensing where extremely high sensitivity is a priority, since even minimal chemical interaction causes noticeable changes inelectrical conductivity, which can be used for the sensor readout. However, the sensitivity has to becomplemented with selectivity, and, for many applications, improved response- and recovery times are needed. This has been addressed, for example, by combining graphene (for sensitivity) with metal/oxides (for selectivity) nanoparticles (NP). On the other hand, functionalization or modification of the graphene often results in poor reproducibility. In this study, we investigate thegas sensing performance of epitaxial graphene on SiC (EG/SiC) decorated with nanostructured metallic layers as well as metal-oxide nanoparticles deposited using scalable thin-film depositiontechniques, like hollow-cathode pulsed plasma sputtering. Under the right modification conditions the electronic properties of the surface remain those of graphene, while the surface chemistry can betuned to improve sensitivity, selectivity and speed of response to several gases relevant for airquality monitoring and control, such as nitrogen dioxide, benzene, and formaldehyde.
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| 22. |
- Eriksson, Peter, 1989-
(författare)
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Cerium Oxide Nanoparticles and Gadolinium Integration : Synthesis, Characterization and Biomedical Applications
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A challenging task, in the area of magnetic resonance imaging is to develop contrast enhancers with built-in antioxidant properties. Oxidative stress is considered to be involved in the onset and progression of several serious conditions such as Alzheimer’s and Parkinson’s disease, and the possibility to use cerium-contained nanoparticles to modulate such inflammatory response has gained a lot of interest lately. The rare earth element gadolinium is, due to its seven unpaired f-electrons and high symmetry of the electronic state, a powerful element for contrast enhancement in magnetic resonance imaging. Chelates based on gadolinium are the most commonly used contrast agents worldwide. When introducing external contrast agents there is always a risk that it may trigger inflammatory responses, why there is an urgent need for new, tailor-made contrast agents.Small sized cerium oxide nanoparticles have electronic structures that allows coexistence of oxidation states 3+ and 4+ of cerium, which correlates to applicable redox reactions in biomedicine. Such cerium oxide nanoparticles have recently shown to exhibit antioxidant properties both in vitro and in vivo, via the mechanisms involving enzyme mimicking activity.This PhD project is a comprehensive investigation of cerium oxide nanoparticles as scaffold materials for gadolinium integration. Gadolinium is well adopted into the crystal structure of cerium oxide, enabling the combination of diagnostic and therapeutic properties into a single nanoparticle. The main focus of this thesis project is to design cerium oxide nanoparticles with gadolinium integration. A stepwise approach was employed as follows: 1) synthesis with controlled integration of gadolinium, 2) material characterization by means of composition crystal structure, size, and size distribution and 3) surface modification for stabilization. The obtained nanoparticles exhibit remarkable antioxidant capability in vitro and in vivo. They deliver strongly enhanced contrast per gadolinium in magnetic resonance imaging, compared to commercially available contrast agents.A soft shell of dextran is introduced to encapsulate the cerium oxide nanoparticles with integrated gadolinium, which protects and stabilizes the hard core and to increases their biocompatibility. The dextran-coating is clearly shown to reduce formation of a protein corona and it improves the dispersibility of the nanoparticles in cell media. Functionalization strategies are currently being studied to endow these nanoparticles with specific tags for targeting purposes. This will enable guidance of the nanoparticles to a specific tissue, for high local magnetic resonance contrast complemented with properties for on-site reduced inflammation.In conclusion, our cerium oxide nanoparticles with integrated gadolinium, exhibit combined therapeutic and diagnostic, i.e. theragnostic capabilities. This type of nanomaterial is highly promising for applications in the field of biomedical imaging.
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| 23. |
- Eriksson, Peter, et al.
(författare)
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Cerium oxide nanoparticles with antioxidant capabilities and gadolinium integration for MRI contrast enhancement
- 2018
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The chelating gadolinium-complex is routinely used as magnetic resonance imaging (MRI) -contrast enhancer. However, several safety issues have recently been reported by FDA and PRAC. There is an urgent need for the next generation of safer MRI-contrast enhancers, with improved local contrast and targeting capabilities. Cerium oxide nanoparticles (CeNPs) are designed with fractions of up to 50% gadolinium to utilize the superior MRI-contrast properties of gadolinium. CeNPs are well-tolerated in vivo and have redox properties making them suitable for biomedical applications, for example scavenging purposes on the tissue-and cellular level and during tumor treatment to reduce in vivo inflammatory processes. Our near edge X-ray absorption fine structure (NEXAFS) studies show that implementation of gadolinium changes the initial co-existence of oxidation states Ce3+ and Ce4+ of cerium, thereby affecting the scavenging properties of the nanoparticles. Based on ab initio electronic structure calculations, we describe the most prominent spectral features for the respective oxidation states. The as-prepared gadolinium-implemented CeNPs are 3-5 nm in size, have r(1)-relaxivities between 7-13 mM(-1) s(-1) and show clear antioxidative properties, all of which means they are promising theranostic agents for use in future biomedical applications.
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| 24. |
- Eriksson, Peter, et al.
(författare)
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Cerium Oxide Nanoparticles with Entrapped Gadolinium for High T-1 Relaxivity and ROS-Scavenging Purposes
- 2022
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Ingår i: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 7:24, s. 21337-21345
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Tidskriftsartikel (refereegranskat)abstract
- Gadolinium chelates are employed worldwide today as clinical contrast agents for magnetic resonance imaging. Until now, the commonly used linear contrast agents based on the rare-earth element gadolinium have been considered safe and well-tolerated. Recently, concerns regarding this type of contrast agent have been reported, which is why there is an urgent need to develop the next generation of stable contrast agents with enhanced spin-lattice relaxation, as measured by improved T-1 relaxivity at lower doses. Here, we show that by the integration of gadolinium ions in cerium oxide nanoparticles, a stable crystalline 5 nm sized nanoparticulate system with a homogeneous gadolinium ion distribution is obtained. These cerium oxide nanoparticles with entrapped gadolinium deliver strong T-1 relaxivity per gadolinium ion (T-1 relaxivity, r(1) = 12.0 mM(-1) s(-1)) with the potential to act as scavengers of reactive oxygen species (ROS). The presence of Ce3+ sites and oxygen vacancies at the surface plays a critical role in providing the antioxidant properties. The characterization of radial distribution of Ce3+ and Ce4+ oxidation states indicated a higher concentration of Ce3+ at the nanoparticle surfaces. Additionally, we investigated the ROS-scavenging capabilities of pure gadolinium-containing cerium oxide nanoparticles by bioluminescent imaging in vivo, where inhibitory effects on ROS activity are shown.
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| 25. |
- Eskilsson, Olof, et al.
(författare)
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Self-Assembly of Metal Nanoparticles in Bacterial Cellulose for the Fabrication of Soft Substrate-Supported Catalysts
- 2024
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Ingår i: ACS Applied Nano Materials. - : AMER CHEMICAL SOC. - 2574-0970.
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Tidskriftsartikel (refereegranskat)abstract
- The transition to green and sustainable catalysts necessitates efficient and safe preparation techniques using abundant and renewable resources. Many metal nanoparticles (NPs) are excellent catalysts but suffer from poor colloidal stability. NP immobilization or fabrication of metal nanostructures on solid supports can avoid issues with NP aggregation and facilitate the reuse of catalysts, but it may result in a decrease in the catalytic performance of the NPs. Here, we show that well-defined colloidal silver, gold, and platinum NPs can be self-assembled in bacterial nanocellulose (BC) membranes, yielding BC-NP nanocomposites that are highly catalytically active using the reduction of 4-nitrophenol (4-NP) as a model reaction. The large effective surface area of BC enables the assembly of large quantities of NPs, resulting in materials with excellent catalytic performance. To address the mass transport limitations of reactants through the 3D nanofibrillar BC network, the membranes were dissociated using sonication to produce dispersed nanocellulose fibrils. This process dramatically reduced the time required for the adsorption of the NPs from days to minutes. Moreover, the catalytic performance of the nanofibril-supported NPs was drastically improved. A turnover frequency above 21,000 h(-1) was demonstrated, which is more than one order of magnitude higher than that for previously reported soft substrate-supported AuNP-based catalytic materials. The ease of fabrication, abundance, and low environmental footprint of the support material, along with reusability, stability, and unprecedented catalytic performance, make BC-NP nanocomposites a compelling option for green and sustainable catalysis.
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