Publications by authors named "Kajsa Uvdal"

47 Publications

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.

Nanotoxicology 2021 Sep 1:1-24. Epub 2021 Sep 1.

Research Institutes of Sweden, RISE, Södertälje, Sweden.

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; CeO nanocrystals with 5% or 14% Gd, CoO, and FeO, were characterized by dynamic light scattering and high-resolution transmission electron microscopy. Nanoparticle-binding proteins were identified and screened for HLA-binding peptides . Monocyte interaction with nanoparticle-protein complexes was assessed . Herein, for the first time, immunogenic properties of nanoparticle-binding proteins have been characterized. The present study indicates that especially CoO-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.
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http://dx.doi.org/10.1080/17435390.2021.1966115DOI Listing
September 2021

Tailorable Membrane-Penetrating Nanoplatform for Highly Efficient Organelle-Specific Localization.

Small 2021 Aug 25;17(31):e2101440. Epub 2021 Jun 25.

Department of Physics, Chemistry, and Biology (IFM), Linköping University, Linköping, SE581 83, Sweden.

Given the breadth of currently arising opportunities and concerns associated with nanoparticles for biomedical imaging, various types of nanoparticles have been widely exploited, especially for cellular/subcellular level probing. However, most currently reported nanoparticles either have inefficient delivery into cells or lack specificity for intracellular destinations. The absence of well-defined nanoplatforms remains a critical challenge hindering practical nano-based bio-imaging. Herein, the authors elaborate on a tailorable membrane-penetrating nanoplatform as a carrier with encapsulated actives and decorated surfaces to tackle the above-mentioned issues. The tunable contents in such a versatile nanoplatform offer huge flexibility to reach the expected properties and functions. Aggregation-induced emission luminogen (AIEgen) is applied to achieve sought-after photophysical properties, specific targeting moieties are installed to give high affinity towards different desired organelles, and critical grafting of cell-penetrating cyclic disulfides (CPCDs) to promote cellular uptake efficiency without sacrificing the specificity. Hereafter, to validate its practicability, the tailored nano products are successfully applied to track the dynamic correlation between mitochondria and lysosomes during autophagy. The authors believe that the strategy and described materials can facilitate the development of functional nanomaterials for various life science applications.
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http://dx.doi.org/10.1002/smll.202101440DOI Listing
August 2021

Impact of Amine Additives on Perovskite Precursor Aging: A Case Study of Light-Emitting Diodes.

J Phys Chem Lett 2021 Jul 17;12(25):5836-5843. Epub 2021 Jun 17.

Department of Physics Chemistry and Biology (IFM), Linköping University, Linköping SE-58183, Sweden.

Amines are widely employed as additives for improving the performance of metal halide perovskite optoelectronic devices. However, amines are well-known for their high chemical reactivity, the impact of which has yet to receive enough attention from the perovskite light-emitting diode community. Here, by investigating an unusual positive aging effect of CHNHI/CsI/PbI precursor solutions as an example, we reveal that amines gradually undergo N-formylation in perovskite precursors over time. This reaction is initialized by hydrolysis of dimethylformamide in the acidic chemical environment. Further investigations suggest that the reaction products collectively impact perovskite crystallization and eventually lead to significantly enhanced external quantum efficiency values, increasing from ∼2% for fresh solutions to ≳12% for aged ones. While this case study provides a positive aging effect, a negative aging effect is possible in other perovksite systems. Our findings pave the way for more reliable and reproducible device fabrication and call for further attention to underlying chemical reactions within the perovskite inks once amine additives are included.
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http://dx.doi.org/10.1021/acs.jpclett.1c01349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256416PMC
July 2021

On the Possibility to Resolve Gadolinium- and Cerium-Based Contrast Agents from their CT Numbers in Dual-Energy Computed Tomography.

Radiat Prot Dosimetry 2021 Jun 9. Epub 2021 Jun 9.

Department of Physics, Chemistry and Biology, Linköping University, SE-581 83, Linköping, Sweden.

Cerium oxide nanoparticles with integrated gadolinium have been proved to be useful as contrast agents in magnetic resonance imaging. Of question is their performance in dual-energy computed tomography. The aims of this work are to determine (1) the relation between the computed tomography number and the concentration of the I, Gd or Ce contrast agent and (2) under what conditions it is possible to resolve the type of contrast agent. Hounsfield values of iodoacetic acid, gadolinium acetate and cerium acetate dissolved in water at molar concentrations of 10, 50 and 100 mM were measured in a water phantom using the Siemens SOMATOM Definition Force scanner; gadolinium- and cerium acetate were used as substitutes for the gadolinium-integrated cerium oxide nanoparticles. The relation between the molar concentration of the I, Gd or Ce contrast agent and the Hounsfield value was linear. Concentrations had to be sufficiently high to resolve the contrast agents.
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http://dx.doi.org/10.1093/rpd/ncab078DOI Listing
June 2021

Selective colorimetric detection of copper (II) by a protein-based nanoprobe.

Spectrochim Acta A Mol Biomol Spectrosc 2021 May 13;252:119462. Epub 2021 Jan 13.

Department of Physics, Chemistry and Biology, Linköping University, Linköping 58183, Sweden.

In this work, we report a novel protein-based nanoprobe (PNP) that can be employed for quantitative analysis of Cu in pure water medium and real samples. Structurally, the proposed nanoprobe comprises a biofriendly protein (hen egg-white lysozyme (HEWL)) and a Cu-specific chromogenic agent, where HEWL acts as a nanocarrier encapsulating a structurally tailored rhodamine B derivate. The resulting PNP exhibits a hydrodynamic diameter of ~ 106 nm and efficiently disperses in water, enabling the detection of Cu in pure aqueous systems without the aid of any organic co-solvents. The high sensitivity and selectivity of PNP allow the colorimetric detection of Cu in the presence of other metal interferents with a low detection limit of 160 nM. The satisfying recovery of trace level Cu in environmental samples demonstrate the great potential of employing PNP for the determination of Cu in actual applications. Most importantly, the simple co-grinding method employing proteins and chromogenic agents provides a novel strategy to generate sensing systems that are useful detection of pollutants in aqueous samples.
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http://dx.doi.org/10.1016/j.saa.2021.119462DOI Listing
May 2021

New Tools for Imaging Neutrophils: Work Function Mapping and Element-Specific, Label-Free Imaging of Cellular Structures.

Nano Lett 2021 01 2;21(1):222-229. Epub 2020 Dec 2.

Department of Physics, Chemistry and Biology (IFM), Division of Molecular Surface Physics and Nano Science, Linköping University, Linköping SE-581 83, Sweden.

Photoemission electron microscopy and imaging X-ray photoelectron spectroscopy are today frequently used to obtain chemical and electronic states, chemical shifts, work function profiles within the fields of surface- and material sciences. Lately, because of recent technological advances, these tools have also been valuable within life sciences. In this study, we have investigated the power of photoemission electron microscopy and imaging X-ray photoelectron spectroscopy for visualization of human neutrophil granulocytes. These cells, commonly called neutrophils, are essential for our innate immune system. We hereby investigate the structure and morphology of neutrophils when adhered to gold and silicon surfaces. Energy-filtered imaging of single cells are acquired. The characteristic polymorphonuclear cellular nuclei divided into 2-5 lobes is visualized. Element-specific imaging is achieved based on O 1s, P 2p, C 1s, Si 2p, and N 1s core level spectra, delivering elemental distribution with submicrometer resolution, illustrating the strength of this type of cellular morphological studies.
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http://dx.doi.org/10.1021/acs.nanolett.0c03554DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809688PMC
January 2021

Rapid detection of mercury (II) ions and water content by a new rhodamine B-based fluorescent chemosensor.

Spectrochim Acta A Mol Biomol Spectrosc 2020 Nov 30;241:118657. Epub 2020 Jun 30.

School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, PR China; Division of Molecular Surface Physics & Nanoscience, Department of Physics, Chemistry and Biology, Linköping University, Linköping 58183, Sweden. Electronic address:

A rhodamine B-based sensor (RS) was designed and synthesized by a combination of the spirolacton rhodamine B (fluorophore) and multidentate chelates (ionophore) with high affinity towards Hg. In the presence of Hg, the resulting red-orange fluorescence (under UV light) and naked eye red color of RS are supposed to be used for quantitative and qualitative measurement of Hg. Further fluorescent titration and analysis demonstrate that RS can selectively detect Hg within 1 s with a low limit of detection (LOD) of 16 nM in acetonitrile media, meanwhile, the association constant (K) was calculated to be 0.32 × 10 M. More importantly, the resultant complex (RSHg) of RS and Hg has also been successfully applied to detect limited water content in acetonitrile solution.
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http://dx.doi.org/10.1016/j.saa.2020.118657DOI Listing
November 2020

Integrated Design of Hierarchical [email protected]@[email protected] Nanobox as Anode Material for Enhanced Lithium Storage Performance.

ACS Appl Mater Interfaces 2020 Apr 17;12(17):19768-19777. Epub 2020 Apr 17.

Shanghai Applied Radiation Institute, School of Environmental and Chemical Engineering, Shanghai University, Shanghai 200444, China.

Transition-metal oxides (TMOs) are potential candidates for anode materials of lithium-ion batteries (LIBs) due to their high theoretical capacity (∼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 [email protected]@[email protected] hierarchical nanobox (CNMN) is then proposed and fabricated to solve those issues. The as-prepared nanobox contains hollow cubic CoSnO 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 CoSnO and MnO efficiently increase the specific capacity. Notably, the dual-layer structure of N-doped carbons plays a critical functional role 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 5C, 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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http://dx.doi.org/10.1021/acsami.9b22368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304665PMC
April 2020

Light-Up Lipid Droplets Dynamic Behaviors Using a Red-Emitting Fluorogenic Probe.

Anal Chem 2020 03 24;92(5):3613-3619. Epub 2020 Feb 24.

Department of Physics, Chemistry and Biology, Linköping University, Linköping 58183, Sweden.

Intracellular lipid metabolism occurs in lipid droplets (LDs), which is critical to the survival of cells. Imaging LDs is an intuitive way to understand their physiology in live cells. However, this is limited by the availability of specific probes that can properly visualize LDs in vivo. Here, an LDs-specific red-emitting probe is proposed to address this need, which is not merely with an ultrahigh signal-to-noise (S/N) ratio and a large Stokes shift (up to 214 nm) but also with superior resistance to photobleaching. The probe has been successfully applied to real-time tracking of intracellular LDs behaviors, including fusion, migration, and lipophagy processes. We deem that the proposed probe here offers a new possibility for deeper understanding of LDs-associated behaviors, elucidation of their roles and mechanisms in cellular metabolism, and determination of the transition between adaptive lipid storage and lipotoxicity as well.
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http://dx.doi.org/10.1021/acs.analchem.9b04410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307831PMC
March 2020

Ratiometric fluorogenic determination of endogenous hypochlorous acid in living cells.

Spectrochim Acta A Mol Biomol Spectrosc 2019 Aug 15;219:232-239. Epub 2019 Apr 15.

School of Environmental and Chemical Engineering, Shanghai University, Shanghai, 200444, PR China; Division of Molecular Surface Physics & Nanoscience, Department of Physics, Chemistry and Biology, Linköping University, Linköping 58183, Sweden. Electronic address:

Hypochlorous acid (HClO) is one of the most important ROS (reactive oxygen species) and common pollutant in tap-water. However, the determination of HClO with fast response and high sensitivity/selectivity is still an urgent demanding. Here we fabricated a ratiometric fluorescent probe RC based on TBET (through-bond energy transfer) on the platform of coumarin and rhodamine with the thiosemicarbazide group as the linker. This probe could display the characteristic fluorescence emission of coumarin. Upon addition of HClO, the linker was reacted into an oxadiazole, resulting in the opening of spiro-ring of rhodamine. The resultant then gives ratiometric fluorogenic changes. The probe exhibits fast response and high selectivity and sensitivity towards HClO with a low limit of detection (~140 nM). Eventually, RC is successfully applicated for determining spiked HClO in water samples and imaging endogenous HClO in living cells.
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http://dx.doi.org/10.1016/j.saa.2019.04.024DOI Listing
August 2019

Hybrid Rhodamine Fluorophores in the Visible/NIR Region for Biological Imaging.

Angew Chem Int Ed Engl 2019 10 11;58(40):14026-14043. Epub 2019 Jun 11.

Key Laboratory of Flexible Electronics (KLOFE) & Institute of Advanced Materials (IAM), Jiangsu National Synergetic Innovation Center for Advanced Materials (SICAM), Nanjing Tech University, Nanjing, 211816, P. R. China.

Fluorophores and probes are invaluable for the visualization of the location and dynamics of gene expression, protein expression, and molecular interactions in complex living systems. Rhodamine dyes are often used as scaffolds in biological labeling and turn-on fluorescence imaging. To date, their absorption and emission spectra have been expanded to cover the entire near-infrared region (650-950 nm), which provides a more suitable optical window for monitoring biomolecular production, trafficking, and localization in real time. This review summarizes the development of rhodamine fluorophores since their discovery and provides strategies for modulating their absorption and emission spectra to generate specific bathochromic-shifts. We also explain how larger Stokes shifts and dual-emissions can be obtained from hybrid rhodamine dyes. These hybrid fluorophores can be classified into various categories based on structural features including the alkylation of amidogens, the substitution of the O atom of xanthene, and hybridization with other fluorophores.
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http://dx.doi.org/10.1002/anie.201901061DOI Listing
October 2019

Graphene Decorated with Iron Oxide Nanoparticles for Highly Sensitive Interaction with Volatile Organic Compounds.

Sensors (Basel) 2019 Feb 22;19(4). Epub 2019 Feb 22.

Applied Sensor Science Unit, IFM, Linköping University, 58183 Linköping, Sweden.

Gases, such as nitrogen dioxide, formaldehyde and benzene, are toxic even at very low concentrations. However, so far there are no low-cost sensors available with sufficiently low detection limits and desired response times, which are able to detect them in the ranges relevant for air quality control. In this work, we address both, detection of small gas amounts and fast response times, using epitaxially grown graphene decorated with iron oxide nanoparticles. This hybrid surface is used as a sensing layer to detect formaldehyde and benzene at concentrations of relevance (low parts per billion). The performance enhancement was additionally validated using density functional theory calculations to see the effect of decoration on binding energies between the gas molecules and the sensor surface. Moreover, the time constants can be drastically reduced using a derivative sensor signal readout, allowing the sensor to work at detection limits and sampling rates desired for air quality monitoring applications.
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http://dx.doi.org/10.3390/s19040918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6413193PMC
February 2019

LTCC Packaged Ring Oscillator Based Sensor for Evaluation of Cell Proliferation.

Sensors (Basel) 2018 Oct 7;18(10). Epub 2018 Oct 7.

Division of Sensor and Actuator Systems, Department of Physics, Chemistry and Biology, Linköping University, SE-58183 Linköping, Sweden.

A complementary metal-oxide-semiconductor (CMOS) chip biosensor was developed for cell viability monitoring based on an array of capacitance sensors utilizing a ring oscillator. The chip was packaged in a low temperature co-fired ceramic (LTCC) module with a flip chip bonding technique. A microcontroller operates the chip, while the whole measurement system was controlled by PC. The developed biosensor was applied for measurement of the proliferation stage of adherent cells where the sensor response depends on the ratio between healthy, viable and multiplying cells, which adhere onto the chip surface, and necrotic or apoptotic cells, which detach from the chip surface. This change in cellular adhesion caused a change in the effective permittivity in the vicinity of the sensor element, which was sensed as a change in oscillation frequency of the ring oscillator. The sensor was tested with human lung epithelial cells (BEAS-2B) during cell addition, proliferation and migration, and finally detachment induced by trypsin protease treatment. The difference in sensor response with and without cells was measured as a frequency shift in the scale of 1.1 MHz from the base frequency of 57.2 MHz. Moreover, the number of cells in the sensor vicinity was directly proportional to the frequency shift.
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http://dx.doi.org/10.3390/s18103346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209925PMC
October 2018

Cerium oxide nanoparticles with antioxidant capabilities and gadolinium integration for MRI contrast enhancement.

Sci Rep 2018 05 3;8(1):6999. Epub 2018 May 3.

Division of Molecular Surface Physics and Nanoscience, Department of Physics, Chemistry and Biology (IFM), Linköping University, SE-581 83, Linköping, Sweden.

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 Ce and Ce 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-relaxivities between 7-13 mM s and show clear antioxidative properties, all of which means they are promising theranostic agents for use in future biomedical applications.
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http://dx.doi.org/10.1038/s41598-018-25390-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5934375PMC
May 2018

A novel Schiff base derivative: Synthesis, two-photon absorption properties and application for bioimaging.

Spectrochim Acta A Mol Biomol Spectrosc 2018 Jun 13;198:304-308. Epub 2018 Mar 13.

Division of Molecular Surface Physics & Nanoscience, Department of Physics, Chemistry and Biology (IFM), Linköing University, 58183 Linköing, Sweden. Electronic address:

A novel donor-π-acceptor-π-donor type (D-π-A-π-D') Schiff base derivative (L) has been designed and synthesized. The structure of L is confirmed by single-crystal X-ray diffraction analysis as well. The photophysical properties of compound L were comprehensively investigated by using both experimental and theoretical methods. The results indicate that L exhibits large Stokes shift and moderate two-photon action (2PA) cross-section in the near infrared (NIR) region. Furthermore, the confocal microscopy imaging study demonstrates that compound L could penetrate into cells and target the cellular mitochondria compartment. Due to its low cytotoxicity, compound L provides a promising tool for directly lighting up the mitochondria compartment in living HepG2 cells.
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http://dx.doi.org/10.1016/j.saa.2018.03.039DOI Listing
June 2018

A reversible and highly selective two-photon fluorescent "on-off-on" probe for biological Cu detection.

Org Biomol Chem 2018 03;16(13):2264-2268

Department of Chemistry, Anhui Provincial Engineering Research Center for Polysaccharide Drugs, Wannan Medical college, Wuhu, 241002, P.R. China.

A two-photon active probe for physiological copper (Cu2+) detection is expected to play an important role in monitoring biological metabolism. Herein, a novel Schiff base derivative (E)-2,2'-((4-((4-(diethylamino)-2-hydroxybenzylidene)amino)phenyl)azanediyl)bis(ethan-1-ol) (L) with remarkable two-photon activity was developed and synthetically investigated. L presents high selectivity and sensitivity for Cu2+ sensing in ethanol/HEPES buffer (v/v, 1 : 1), which is accompanied by the fluorescence switching "off" and subsequently "on" with the addition of EDTA. The mechanism for the detection of Cu2+ is further analyzed using 1H NMR titration, mass spectra and theoretical calculations. Furthermore, since the probe L possesses good photophysical properties, excellent biocompatibility and low cytotoxicity, it is successfully applied to track Cu2+ in the cellular endoplasmic reticulum by two-photon fluorescence imaging, showing its potential value for practical applications in biological systems.
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http://dx.doi.org/10.1039/c8ob00257fDOI Listing
March 2018

Imaging XPS and photoemission electron microscopy; surface chemical mapping and blood cell visualization.

Biointerphases 2017 05 2;12(2):02C408. Epub 2017 May 2.

Department of Physics, Chemistry and Biology (IFM), Division of Molecular Surface Physics and Nano Science, Linköping University, Linköping SE-581 83, Linköping, Sweden.

Combined photoemission electron microscopy (PEEM) and imaging x-ray photoelectron spectroscopy (XPS), i.e., electron spectroscopy for chemical analysis in the nanoregion, has been used for surface characterization of bio-relevant and biological samples. In the first example, the authors prepared a gold patterned silicon substrate, stepwise surface modified by self-assembled monolayers followed by quantum dot (QDot) specific linking and investigated by means of work function mapping and elemental imaging in the submicrometer range. Spatially resolved core level images of C1s, V2p, and Y3d are obtained, which verify the selective thiol adsorption on the gold squares and specific binding of europium doped yttrium vanadate QDots on the self-assembled monolayer. The second example is platelet adhesion to Immunoglobulin G modified silicon surfaces, investigated by means of laterally resolved PEEM. Images of platelets clearly show activated cells with a morphology change including an enlarged surface area and elongated pseudopodia, with a lateral resolution of 140 nm. In the last example, neutrophils were allowed to attach to plain silicon surfaces and investigated by means of PEEM and imaging XPS. Here, the cells show a round shaped morphology, as expected. Threshold imaging with work function contrast is used to localize the area of interest, followed by elemental specific mapping on cells in the submicrometer region. Chemical shifts of C1s in photoemission are used to distinguish vital parts of the cell structure. The strong C1s (C-C) signal is achieved from the region of the cell membrane, i.e., high density of phospholipids, while C1s (C-N) and C1s (C-O) signals are obtained from the core of the cell, in good agreement with the presence of cytoplasm and deoxyribonucleic acid containing cell nucleus. The combination of PEEM and imaging XPS is shown here as a tool to deliver new insight into biological samples, i.e., a rapid sample overview is obtained based on low energy secondary electrons with work function contrast, followed by detailed studies in the narrow mode for elemental compositions based on photoemission. This study illustrates the strength of combined PEEM and XPS in the imaging mode on cell studies.
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http://dx.doi.org/10.1116/1.4982644DOI Listing
May 2017

Probe for simultaneous membrane and nucleus labeling in living cells and bioimaging using a two-photon absorption water-soluble Zn(ii) terpyridine complex with a reduced π-conjugation system.

Chem Sci 2017 Jan 3;8(1):142-149. Epub 2016 Aug 3.

Department of Chemistry , Key Laboratory of Functional Inorganic Material Chemistry of Anhui Province , Anhui University , Hefei 230039 , P. R. China . Email: ; Email:

Small, biocompatible and water-soluble molecules with high two-photon absorption (2PA) cross-section values () are in high demand for specific bioimaging applications. Here, two novel terpyridine derivative ligands with donor-acceptor (D-A) () and donor-π-acceptor (D-π-A) () models, and their corresponding Zn(ii) complexes are designed and characterized. It was found that the two-photon absorption cross section values () in the near-infrared region (NIR, about 800 nm) are significantly enhanced for complexes and compared to their free D-A type ligand , while those of complexes and were greatly decreased relative to their free ligand , thus confirming that the smaller ligand (D-A type) displays a suitable Turn-ON fluorescence pair for two-photon fluorescence microscopy (2PFM). Firstly, the potential of simultaneously labeling a live cell plasma membrane and nucleus using complex is demonstrated. In addition, live larval and adult zebrafish incubated with an optimal concentration of demonstrated clear brain uptake. Lastly and importantly, using such a probe to visualize the blood-brain-barrier (BBB) capillary endothelial cells and penetrate the BBB into the central nervous system (CNS) intravenously in a mouse model is also explored.
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http://dx.doi.org/10.1039/c6sc02342hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5308395PMC
January 2017

A TPA-caged precursor of (imino)coumarin for "turn-on" fluorogenic detection of Cu(.).

Anal Chim Acta 2016 Aug 1;933:189-95. Epub 2016 Jun 1.

Division of Molecular Surface Physics & Nanoscience, Department of Physics, Chemistry and Biology, Linköping University, Linköping 58183, Sweden.

We strategize to utilize the precursors of (imino)coumarin fluorophores to deliver novel reactive Cu(+) probes, where tris[(2-pyridyl)-methyl] amine (TPA) works as a reactive receptor towards Cu(+). To verify this strategy, CP1, a representative probe and relevant sensing behaviors towards Cu(+) are presented here. CP1 features good solubility and fast response for monitoring labile copper in aqueous solution and live cells. The sensing mechanism of CP1 is determined by HPLC titration and mass spectrometric analysis. The probe CP1 exhibits a 60-fold fluorescence enhancement and a detection limitation of 10.8 nM upon the detection of Cu(+). CP1 is further applied for imaging labile copper in live cells. This work provides a starting point for future development of Cu(+) probes, based on in situ formation of (imino)coumarin scaffolds, as well as their further investigations of copper signaling and biological events.
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http://dx.doi.org/10.1016/j.aca.2016.05.031DOI Listing
August 2016

A logic gate-based fluorogenic probe for Hg(2+) detection and its applications in cellular imaging.

Anal Chim Acta 2016 May 19;919:85-93. Epub 2016 Mar 19.

Division of Molecular Surface Physics & Nanoscience, Department of Physics, Chemistry and Biology, Linköping University, Linköping, 58183, Sweden.

A new colorimetric and fluorogenic probe (RN3) based on rhodamine-B has been successfully designed and synthesized. It displays a selective response to Hg(2+) in the aqueous buffer solution over the other competing metals. Upon addition of Hg(2+), the solution of RN3 exhibits a 'naked eye' observable color change from colorless to red and an intensive fluorescence with about 105-fold enhancement. The changes in the color and fluorescence are ascribed to the ring-opening of spirolactam in rhodamine fluorophore, which is induced by a binding of the constructed receptor to Hg(2+) with the association and dissociation constants of 0.22 × 10(5) M(-1) and 25.2 μM, respectively. The Job's plot experiment determines a 1:1 binding stoichiometry between RN3 and Hg(2+). The resultant "turn-on" fluorescence in buffer solution, allows the application of a method to determine Hg(2+) levels in the range of 4.0-15.0 μM, with the limit of detection (LOD) calculated at 60.7 nM (3σ/slope). In addition, the fluorescence 'turn-off' and color 'fading-out' happen to the mixture of RN3-Hg(2+) by further addition of I(-) or S(2-). The reversible switching cycles of fluorescence intensity upon alternate additions of Hg(2+) and S(2-) demonstrate that RN3 can perform as an INHIBIT logic gate. Furthermore, the potential of RN3 as a fluorescent probe has been demonstrated for cellular imaging.
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http://dx.doi.org/10.1016/j.aca.2016.03.017DOI Listing
May 2016

A series of Zn(ii) terpyridine complexes with enhanced two-photon-excited fluorescence for in vitro and in vivo bioimaging.

J Mater Chem B 2015 Sep 19;3(36):7213-7221. Epub 2015 Aug 19.

Department of Chemistry, Key Laboratory of Functional Inorganic Materials Chemistry of Anhui Province, Anhui University, Hefei 230039, P. R. China.

It is still a challenge to obtain two-photon excited fluorescent bioimaging probes with intense emission, high photo-stability and low cytotoxicity. In the present work, four Zn(ii)-coordinated complexes (1-4) constructed from two novel D-A and D-π-A ligands (L and L) are investigated both experimentally and theoretically, aiming to explore efficient two-photon probes for bioimaging. Molecular geometry optimization used for theoretical calculations is achieved using the crystallographic data. Notably, the results indicate that complexes 1 and 2 display enhanced two-photon absorption (2PA) cross sections compared to their corresponding D-A ligand (L). Furthermore, it was found that complex 1 has the advantages of moderate 2PA cross section in the near-infrared region, longer fluorescence lifetime, higher quantum yield, good biocompatibility and enhanced two-photon excited fluorescence. Therefore, complex 1 is evaluated as a bioimaging probe for in vitro imaging of HepG2 cells, in which it is observed under a two-photon scanning microscope that complex 1 exhibits effective co-staining with endoplasmic reticulum (ER) and nuclear membrane; as well as for in vivo imaging of zebrafish larva, in which it is observed that complex 1 exhibits specificity in the intestinal system.
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http://dx.doi.org/10.1039/c5tb01185jDOI Listing
September 2015

Magneto-fluorescent nanoparticles with high-intensity NIR emission, T- and T-weighted MR for multimodal specific tumor imaging.

J Mater Chem B 2015 Apr 9;3(15):3072-3080. Epub 2015 Mar 9.

College of Pharmacy & The Key Laboratory for Medical Tissue Engineering of Liaoning Province, Liaoning Medical University, Jinzhou, 121001, China.

Nanoparticles exhibiting bright near-infrared (NIR) fluorescence, T- and T-weighted MR were synthesized for specific tumor imaging. Clinically used FeO nanoparticles exhibit an intrinsic dark signal (T-weighted MRI), which sometimes misleads clinical diagnosis. Here, for the first time we integrated ultrasmall FeO nanoparticles (2-3 nm) with an NIR emitting semiconducting polymer for both T- and T-weighted MRI as well as fluorescence imaging of tumors. Bio-functionalized multi-modality fluorescent magnetic nanoparticles (FMNPs) functionalized with folic acid exhibit bright fluorescence and high relaxation (r = 7.008 mM s, r = 26.788 mM s, r/r = 3.8). These FMNPs have a small average dynamic size of about 20 nm with low aggregation and long circulation time. In vitro studies revealed that FMNPs can serve as an effective fluorescent probe to achieve targeting images of human A549 lung cancer cells without obvious cytotoxicity. In vivo experimental results show that the FMNPs are able to preferentially accumulate in tumor tissues for specific fluorescence imaging, T- and T-weighted MRI.
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http://dx.doi.org/10.1039/c5tb00155bDOI Listing
April 2015

A facile "click" reaction to fabricate a FRET-based ratiometric fluorescent Cu probe.

J Mater Chem B 2014 Jul 11;2(28):4467-4472. Epub 2014 Jun 11.

State Key Laboratory of Pollution Control and Resource Reuse, Tongji University, Siping Rd 1239, Shanghai, 200092, P.R. China.

A facile one-step Cu(i)-catalyzed "click" reaction, between a dansyl-azide and a propargyl-substituted rhodamine B hydrazide, is employed to fabricate a novel FRET ratiometric "off-on" fluorescent probe. The sensitive emission of the donor, a dansyl group, overlaps perfectly with the absorption of the acceptor, xanthene in the open-ring rhodamine. The proposed probe shows high selectivity towards Cu. The ratio of emission intensities at 568 and 540 nm (I/I) exhibits a drastic 28-fold enhancement upon addition of Cu. The probe shows an excellent linear relationship between emission ratios and the concentrations of Cu from 10 to 50 μM, with a detection limit (S/N = 3) of 0.12 μM. The preliminary cellular studies demonstrated that the probe is cell membrane permeable and could be applied for ratiometric fluorescence imaging of intracellular Cu with almost no cytotoxicity. The ingenuity of the probe design is to construct a FRET donor-acceptor interconnector and a selective receptor simultaneously by "click" reaction. The strategy was verified to have great potential for developing novel FRET probes for Cu.
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http://dx.doi.org/10.1039/c4tb00441hDOI Listing
July 2014

One-step synthesis of water-dispersible ultra-small Fe3O4 nanoparticles as contrast agents for T1 and T2 magnetic resonance imaging.

Nanoscale 2014 Mar 31;6(5):2953-63. Epub 2014 Jan 31.

Department of Chemistry, College of Pharmacy, Liaoning Medical University, Jinzhou, 121001, China.

Uniform, highly water-dispersible and ultra-small Fe3O4 nanoparticles were synthesized via a modified one-step coprecipitation approach. The prepared Fe3O4 nanoparticles not only show good magnetic properties, long-term stability in a biological environment, but also exhibit good biocompatibility in cell viability and hemolysis assay. Due to the ultra-small sized and highly water-dispersibility, they exhibit excellent relaxivity properties, the 1.7 nm sized Fe3O4 nanoparticles reveal a low r2/r1 ratio of 2.03 (r1 = 8.20 mM(-1) s(-1), r2 = 16.67 mM(-1) s(-1)); and the 2.2 nm sized Fe3O4 nanoparticles also appear to have a low r2/r1 ratio of 4.65 (r1 = 6.15 mM(-1) s(-1), r2 = 28.62 mM(-1) s(-1)). This demonstrates that the proposed ultra-small Fe3O4 nanoparticles have great potential as a new type of T1 magnetic resonance imaging contrast agents. Especially, the 2.2 nm sized Fe3O4 nanoparticles, have a competitive r1 value and r2 value compared to commercial contrasting agents such as Gd-DTPA (r1 = 4.8 mM(-1) s (-1)), and SHU-555C (r2 = 69 mM(-1) s(-1)). In vitro and in vivo imaging experiments, show that the 2.2 nm sized Fe3O4 nanoparticles exhibit great contrast enhancement, long-term circulation, and low toxicity, which enable these ultra-small sized Fe3O4 nanoparticles to be promising as T1 and T2 dual contrast agents in clinical settings.
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http://dx.doi.org/10.1039/c3nr05550gDOI Listing
March 2014

Highly water-dispersible surface-modified Gd(2)O(3) nanoparticles for potential dual-modal bioimaging.

Chemistry 2013 Sep;19(38):12658-67

Water-dispersible and luminescent gadolinium oxide (GO) nanoparticles (NPs) were designed and synthesized for potential dual-modal biological imaging. They were obtained by capping gadolinium oxide nanoparticles with a fluorescent glycol-based conjugated carboxylate (HL). The obtained nanoparticles (GO-L) show long-term colloidal stability and intense blue fluorescence. In addition, L can sensitize the luminescence of europium(III) through the so-called antenna effect. Thus, to extend the spectral ranges of emission, europium was introduced into L-modified gadolinium oxide nanoparticles. The obtained EuIII-doped particles (Eu:GO-L) can provide visible red emission, which is more intensive than that without L capping. The average diameter of the monodisperse modified oxide cores is about 4 nm. The average hydrodynamic diameter of the L-modified nanoparticles was estimated to be about 13 nm. The nanoparticles show effective longitudinal water proton relaxivity. The relaxivity values obtained for GO-L and Eu:GO-L were r1=6.4 and 6.3 s−1 mM−1 with r2/r1 ratios close to unity at 1.4 T. Longitudinal proton relaxivities of these nanoparticles are higher than those of positive contrast agents based on gadolinium complexes such as Gd-DOTA, which are commonly used for clinical magnetic resonance imaging. Moreover, these particles are suitable for cellular imaging and show good biocompatibility.
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http://dx.doi.org/10.1002/chem.201301687DOI Listing
September 2013

High-intensity near-IR fluorescence in semiconducting polymer dots achieved by cascade FRET strategy.

Chem Sci 2013 May 27;4(5):2143-2151. Epub 2013 Feb 27.

Division of Molecular Surface Physics & Nanoscience, Department of Physics, Chemistry, and Biology, Linköping University, Linköping 58183, Sweden.

Near-IR (NIR) emitting semiconducting polymer dots (Pdots) with ultrabright fluorescence have been prepared for specific cellular targeting. A series of π-conjugated polymers were synthesized to form water dispersible multicomponent Pdots by an ultrasonication-assisted co-precipitation method. By optimizing cascade energy transfer in Pdots, high-intensity NIR fluorescence ( = 0.32) with tunable excitations, large absorption-emission separation (up to 330 nm), and narrow emission bands (FWHM = 44 nm) have been achieved. Single-particle fluorescence imaging show that the as-prepared NIR Pdots were more than three times brighter than the commercially available Qdot705 with comparable sizes under identical conditions of excitation and detection. Because of the covalent introduction of carboxylic acid groups into polymer side chains, the bioconjugation between NIR-emitting Pdots and streptavidins can be readily completed these functional groups on the surface of Pdots. Furthermore, through flow cytometry and confocal fluorescence microscopy the NIR-emitting Pdot-streptavidin conjugates proved that they could effectively label EpCAM receptors on the surface of MCF-7 cells, specific binding between streptavidin and biotin.
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http://dx.doi.org/10.1039/C3SC50222HDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5613671PMC
May 2013

Multicolor fluorescent semiconducting polymer dots with narrow emissions and high brightness.

ACS Nano 2013 Jan 2;7(1):376-84. Epub 2013 Jan 2.

Department of Chemistry, University of Washington, Seattle, Washington 98195, USA.

Fluorescent semiconducting polymer dots (Pdots) have attracted great interest because of their superior characteristics as fluorescent probes, such as high fluorescence brightness, fast radiative rates, and excellent photostability. However, currently available Pdots generally exhibit broad emission spectra, which significantly limit their usefulness in many biological applications involving multiplex detections. Here, we describe the design and development of multicolor narrow emissive Pdots based on different boron dipyrromethene (BODIPY) units. BODIPY-containing semiconducting polymers emitting at multiple wavelengths were synthesized and used as precursors for preparing the Pdots, where intraparticle energy transfer led to highly bright, narrow emissions. The emission full width at half-maximum of the resulting Pdots varies from 40 to 55 nm, which is 1.5-2 times narrower than those of conventional semiconducting polymer dots. BODIPY 520 Pdots were about an order of magnitude brighter than commercial Qdot 525 under identical laser excitation conditions. Fluorescence imaging and flow cytometry experiments indicate that the narrow emissions from these bright Pdots are promising for multiplexed biological detections.
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http://dx.doi.org/10.1021/nn304376zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3552064PMC
January 2013

Effects of gadolinium oxide nanoparticles on the oxidative burst from human neutrophil granulocytes.

Nanotechnology 2012 Jul 18;23(27):275101. Epub 2012 Jun 18.

Division of Molecular Surface Physics and Nanoscience, Department of Physics, Chemistry and Biology, Linköping University, SE-581 83 Linköping, Sweden.

We have previously shown that gadolinium oxide (Gd(2)O(3)) 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 Gd(2)O(3) nanoparticles on the production of reactive oxygen species (ROS) from human neutrophils, by means of luminol-dependent chemiluminescence. Three sets of Gd(2)O(3) nanoparticles were studied, i.e. as synthesized, dialyzed and both PEG-functionalized and dialyzed Gd(2)O(3) 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 Gd(2)O(3) nanoparticle exposure indicates that these nanoparticles are promising candidates for MR-imaging purposes.
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http://dx.doi.org/10.1088/0957-4484/23/27/275101DOI Listing
July 2012

Preparation of amyloid-like fibrils containing magnetic iron oxide nanoparticles: effect of protein aggregation on proton relaxivity.

Biochem Biophys Res Commun 2012 Mar 20;419(4):682-6. Epub 2012 Feb 20.

Biomolecular and Organic Electronics, Department of Physics, Chemistry, and Biology (IFM), Linköping University, SE-581 83 Linköping, Sweden.

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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http://dx.doi.org/10.1016/j.bbrc.2012.02.077DOI Listing
March 2012

Gd₂O₃ nanoparticles in hematopoietic cells for MRI contrast enhancement.

Int J Nanomedicine 2011 9;6:3233-40. Epub 2011 Dec 9.

Division of Radiology, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.

As the utility of magnetic resonance imaging (MRI) broadens, the importance of having specific and efficient contrast agents increases and in recent time there has been a huge development in the fields of molecular imaging and intracellular markers. Previous studies have shown that gadolinium oxide (Gd(2)O(3)) nanoparticles generate higher relaxivity than currently available Gd chelates: In addition, the Gd(2)O(3) nanoparticles have promising properties for MRI cell tracking. The aim of the present work was to study cell labeling with Gd(2)O(3) nanoparticles in hematopoietic cells and to improve techniques for monitoring hematopoietic stem cell migration by MRI. Particle uptake was studied in two cell lines: the hematopoietic progenitor cell line Ba/F3 and the monocytic cell line THP-1. Cells were incubated with Gd(2)O(3) nanoparticles and it was investigated whether the transfection agent protamine sulfate increased the particle uptake. Treated cells were examined by electron microscopy and MRI, and analyzed for particle content by inductively coupled plasma sector field mass spectrometry. Results showed that particles were intracellular, however, sparsely in Ba/F3. The relaxation times were shortened with increasing particle concentration. Relaxivities, r(1) and r(2) at 1.5 T and 21°C, for Gd(2)O(3) nanoparticles in different cell samples were 3.6-5.3 s(-1) mM(-1) and 9.6-17.2 s(-1) mM(-1), respectively. Protamine sulfate treatment increased the uptake in both Ba/F3 cells and THP-1 cells. However, the increased uptake did not increase the relaxation rate for THP-1 as for Ba/F3, probably due to aggregation and/or saturation effects. Viability of treated cells was not significantly decreased and thus, it was concluded that the use of Gd(2)O(3) nanoparticles is suitable for this type of cell labeling by means of detecting and monitoring hematopoietic cells. In conclusion, Gd(2)O(3) nanoparticles are a promising material to achieve positive intracellular MRI contrast; however, further particle development needs to be performed.
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http://dx.doi.org/10.2147/IJN.S23940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252671PMC
May 2012
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