Publications by authors named "Alexander Vakurov"

13 Publications

  • Page 1 of 1

Barium yttrium fluoride based upconversion nanoparticles as dual mode image contrast agents.

Mater Sci Eng C Mater Biol Appl 2021 May 6;124:111937. Epub 2021 Feb 6.

School of Chemical and Process Engineering, Faculty of Engineering and Physical Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom.

Dual labeled contrast agents could provide better complementary information for bioimaging than available solely from a single modality. In this paper we investigate the suitability of Yb and Er-doped BaYF upconversion nanoparticles (UCNPs) as both optical and X-ray micro computed tomography (μCT) contrast agents. Stable, aqueous UCNP dispersions were synthesised using a hydrothermal method with the addition of polyethyleneimine (PEI). UCNPs were single crystal and had a truncated cuboidal and/or truncated octahedral morphology, with average particle size of 47 ±9 nm from transmission electron microscopy which was further used to characterize the structure and composition in detail. A zeta potential value of +51 mV was measured for the aqueous nanoparticle dispersions which is beneficial for cell permeability. The outer hydrated PEI layer is also advantageous for the attachment of proteins for targeted delivery in biological systems. The prepared UCNPs were proven to be non-toxic to endothelial cells up to a concentration of 3.5 mg/mL, when assessed using an MTT assay. The particles showed intense green upconversion photoluminescence when excited at a wavelength of 976 nm using a diode laser. Quantitative X-ray μCT contrast imaging confirmed the potential of these UCNPs as X-ray contrast agents and confirming their dual modality for bioimaging.
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http://dx.doi.org/10.1016/j.msec.2021.111937DOI Listing
May 2021

Selective cellular imaging with lanthanide-based upconversion nanoparticles.

J Biophotonics 2019 04 2;12(4):e201800256. Epub 2019 Jan 2.

Leeds Institute for Cardiovascular and Metabolic Medicine (LICAMM), Faculty of Medicine and Health, University of Leeds, Leeds LS2 9JT, UK.

Upconversion nanoparticles (UCNPs) with sodium yttrium fluoride, NaYF (host lattice) doped with Yb (sensitizer) and Er (activator) were synthesized via hydrothermal route incorporating polyethyleneimine (PEI) for their long-term stability in water. The cationic PEI-modified UCNPs with diameter 20 ± 4 nm showed a zeta potential value of +36.5 mV and showed an intense, visible red luminescence and low-intensity green emission with 976 nm laser excitation. The particles proven to be nontoxic to endothelial cells, with a 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) assay, showing 90% to 100% cell viability, across a wide range of UCNP concentrations (0.3 ng/mL-0.3 mg/mL) were used in multiphoton imaging. Multiphoton cellular imaging and emission spectroscopy data reported here prove that the UCNPs dispersed in cell culture media are predominantly concentrated in the cytoplasm than the cell nucleus. The energy transfer from PEI-coated UCNPs to surrounding media for red luminescence in the biological system is also highlighted with spectroscopic measurements. Results of this study propose that UCNPs can, therefore, be used for cytoplasm selective imaging together with multiphoton dyes (eg, 4',6-diamidino-2-phenylindole (DAPI)) that are selective to cell nucleus.
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http://dx.doi.org/10.1002/jbio.201800256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7065621PMC
April 2019

Redox-Dependent Modulation of T-Type Ca(2+) Channels in Sensory Neurons Contributes to Acute Anti-Nociceptive Effect of Substance P.

Antioxid Redox Signal 2016 08;25(5):233-51

1 Department of Pharmacology, Hebei Medical University , Shijiazhuang, P.R. China .

Aims: Neuropeptide substance P (SP) is produced and released by a subset of peripheral sensory neurons that respond to tissue damage (nociceptors). SP exerts excitatory effects in the central nervous system, but peripheral SP actions are still poorly understood; therefore, here, we aimed at investigating these peripheral mechanisms.

Results: SP acutely inhibited T-type voltage-gated Ca(2+) channels in nociceptors. The effect was mediated by neurokinin 1 (NK1) receptor-induced stimulation of intracellular release of reactive oxygen species (ROS), as it can be prevented or reversed by the reducing agent dithiothreitol and mimicked by exogenous or endogenous ROS. This redox-mediated T-type Ca(2+) channel inhibition operated through the modulation of CaV3.2 channel sensitivity to ambient zinc, as it can be prevented or reversed by zinc chelation and mimicked by exogenous zinc. Elimination of the zinc-binding site in CaV3.2 rendered the channel insensitive to SP-mediated inhibition. Importantly, peripherally applied SP significantly reduced bradykinin-induced nociception in rats in vivo; knock-down of CaV3.2 significantly reduced this anti-nociceptive effect. This atypical signaling cascade shared the initial steps with the SP-mediated augmentation of M-type K(+) channels described earlier.

Innovation: Our study established a mechanism underlying the peripheral anti-nociceptive effect of SP whereby this neuropeptide produces ROS-dependent inhibition of pro-algesic T-type Ca(2+) current and concurrent enhancement of anti-algesic M-type K(+) current. These findings will lead to a better understanding of mechanisms of endogenous analgesia.

Conclusion: SP modulates T-type channel activity in nociceptors by a redox-dependent tuning of channel sensitivity to zinc; this novel modulatory pathway contributes to the peripheral anti-nociceptive effect of SP. Antioxid. Redox Signal. 25, 233-251.
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http://dx.doi.org/10.1089/ars.2015.6560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971421PMC
August 2016

The chronic toxicity of CuO nanoparticles and copper salt to Daphnia magna.

J Hazard Mater 2015 30;283:416-22. Epub 2014 Sep 30.

Systemic Physiological and Ecotoxicological Research, Department of Biology, University of Antwerp, Antwerp, Belgium.

In this study, the effects of CuO nanoparticles and CuCl2·2H2O were tested on Daphnia magna under chronic exposure scenarios. During a 21-day exposure to the nanoparticles and salt, the reproduction was followed by a daily count of the number of offspring. After the exposure, the adult Daphnia length and uptake of copper was measured. The dissolved, nanoparticle and aggregated fractions were distinguished in the exposure medium. The results showed that only a small fraction of the nanoparticles dissolved, while the majority of the particles formed large aggregates (>450 nm). The dissolved fraction of the nanoparticles corresponded with the dissolved fraction of the copper salt. The effects of the nanoparticles (reproduction EC10: 0.546 mg Cu/l, EC20: 0.693 mg Cu/l, EC50: 1.041 mg Cu/l) on reproduction and length were much lower than the effects of the copper salts (reproduction EC10: 0.017 mg Cu/l, EC20: 0.019 mg Cu/l, EC50: 0.022 mg Cu/l). Based upon total body analysis, the Daphnia copper concentration appeared much higher when exposed to the nanoparticles than when exposed to the salt. These combined results indicate that the toxicity of CuO nanoparticles to D. magna is caused by copper ions formed during dissolution of the nanoparticles in the exposure medium.
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http://dx.doi.org/10.1016/j.jhazmat.2014.09.037DOI Listing
February 2016

Direct characterization of fluid lipid assemblies on mercury in electric fields.

ACS Nano 2014 Apr 19;8(4):3242-50. Epub 2014 Mar 19.

School of Chemistry, University of Leeds , Leeds, LS2 9JT, U.K.

Phospholipid monolayers on mercury (Hg) surfaces have received substantial and extensive scientific interest not only because of their use as a biomembrane model but also for their application as a successful toxicity-sensing element. The monolayers show characteristic and very reproducible phase transitions manifest as consecutive voltammetric peaks in response to applied transverse electric fields. Unfortunately, apart from the results of simulation studies, there is a lack of data on the lipid phase structures to help interpret these voltammetric peaks. In this paper we report on the direct measurement of the structural changes underlying the phase transitions of phospholipid layers of dioleoyl phosphatidylcholine (DOPC) at electrified Hg surfaces using atomic force microscopy force-distance techniques. These direct measurements enable a description of the following structural changes in fluid lipid assemblies on a liquid electrode within an increasing transverse electric field. At about -1.0 V (vs Ag/AgCl) a field-facilitated ingress of ions and water into the monolayer results in a phase transition to a structured 2D emulsion. This is followed by a further phase transition at more negative potentials involving the readsorption of bilayer patches. At stronger values of field the bilayer patches form semivesicles, which subsequently collapse to form a monolayer of uncertain composition at very negative potentials. The observation that a monolayer on Hg converts to a bilayer by increasing the applied potential has allowed techniques to be developed for preparing and characterizing a near-continuous DOPC bilayer on Hg in an applied potential window within -1.0 and -1.4 V (vs Ag/AgCl).
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http://dx.doi.org/10.1021/nn4037267DOI Listing
April 2014

Electrochemical modelling of QD-phospholipid interactions.

J Colloid Interface Sci 2014 Apr 30;420:9-14. Epub 2013 Dec 30.

School of Chemistry, University of Leeds, Leeds LS2 9JT, UK. Electronic address:

Hypothesis: The aggregation of quantum dots (QDs) and capping of individual QDs affects their activity towards biomembrane models.

Experiments: Electrochemical methods using a phospholipid layer on mercury (Hg) membrane model have been used to determine the phospholipid monolayer activity of thioglycollic acid (TGA) coated quantum dots (QDs) as an indicator of biomembrane activity. The particles were characterised for size and charge.

Findings: The activity of the QDs towards dioleoyl phosphatidylcholine (DOPC) monolayers is pH dependent, and is most active at pH 8.2 within the pH range 8.2-6.5 examined in this work. This pH dependent activity is the result of increased particle aggregation coupled to decreasing surface charge emanating from the TGA carboxylic groups employed to stabilize the QD dispersion in aqueous media. Capping the QDs with CdS/ZnS lowers the particles' activity to phospholipid monolayers.
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http://dx.doi.org/10.1016/j.jcis.2013.12.054DOI Listing
April 2014

Electrochemical screening of biomembrane-active compounds in water.

Anal Chim Acta 2014 Feb 10;813:83-9. Epub 2014 Jan 10.

School of Chemistry, University of Leeds, Leeds LS2 9JT, United Kingdom.

Interactions of biomembrane-active compounds with phospholipid monolayers on microfabricated Pt/Hg electrodes in an on-line high throughput flow system are demonstrated by recording capacitance current peak changes as rapid cyclic voltammograms (RCV). Detection limits of the compounds' effects on the layer have been estimated from the data. Compounds studied include steroids, polycyclic aromatic hydrocarbons, tricyclic antidepressants and tricyclic phenothiazines. The results show that the extent and type of interaction depends on the-(a) presence and number of aromatic rings and substituents, (b) presence and composition of side chains and, (c) molecular shape. Interaction is only indirectly related to compound hydrophobicity. For a selection of tricyclic antidepressants and tricyclic phenothiazines the detection limit in water is related to their therapeutic normal threshold. The sensing assay has been tested in the presence of humic acid as a potential interferent and in a tap water matrix. The system can be applied to the screening of putative hazardous substances and pharmaceuticals allowing for early detection thereof in the water supply. The measurements are made in real time which means that potentially toxic compounds are detected rapidly within <10 min per assay. This technology will contribute greatly to environment safety and health.
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http://dx.doi.org/10.1016/j.aca.2014.01.009DOI Listing
February 2014

The chronic toxicity of ZnO nanoparticles and ZnCl2 to Daphnia magna and the use of different methods to assess nanoparticle aggregation and dissolution.

Nanotoxicology 2014 Nov 29;8(7):709-17. Epub 2013 Jul 29.

Department of Biology (Systemic Physiological and Ecotoxicological Research), University of Antwerp , Antwerp , Belgium.

In this study, the effect of ZnO nanoparticles and ZnCl2 on growth, reproduction and accumulation of zinc in Daphnia magna was determined in a 21-day chronic toxicity test. A variety of techniques were used to distinguish the free zinc ion, dissolved, nanoparticle and aggregated zinc fraction in the Daphnia test medium. The results showed similar chronic effects on growth, reproduction and accumulation for the ZnO nanoparticles (EC10, 20, 50 reproduction: 0.030, 0.049, 0.112 mg Zn/l) and the ZnCl2 (EC10, 20, 50 reproduction: 0.014, 0.027, 0.082 mg Zn/l). A large fraction of the nanoparticles rapidly dissolved after introduction in the exposure medium. Aggregation of nanoparticles was also observed but within 48 h of exposure most of these ZnO aggregates were dissolved. Based on the combined dissolution kinetics and toxicity results, it can be concluded that the toxicological effects of ZnO nanoparticles at the chronic level can be largely attributed to the dissolved fraction rather than the nanoparticles or initially formed aggregates.
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http://dx.doi.org/10.3109/17435390.2013.822594DOI Listing
November 2014

Interaction of imidazolium-based room-temperature ionic liquids with DOPC phospholipid monolayers: electrochemical study.

Langmuir 2013 Jun 23;29(22):6573-81. Epub 2013 May 23.

CIMaINa and Dipartimento di Fisica, Università degli Studi di Milano, Milano, Italy.

To test the biocompatible character of room-temperature ionic liquids (ILs), the interaction of various ILs with biological membrane (biomembrane) models was studied in this work. Dioleoyl phosphatidylcholine (DOPC) adsorbed on a mercury (Hg) electrode forms an impermeable defect-free monolayer which is a well established biomembrane model, prone to be studied by electrochemical techniques. We have monitored the modifications of the Hg supported monolayer caused by ILs using rapid cyclic voltammetry (RCV), alternating current voltammetry (ACV), and electrochemical impedance spectroscopy (EIS). A series of imidazolium-based ILs were investigated whose interaction highlighted the role of anion and lateral side chain of cation during the interaction with DOPC monolayers. It was shown that the hydrophobic and lipophilic character of the IL cations is a primary factor responsible for this interaction. Hg-supported monolayers provide an accurate analysis of the behavior of ILs at the interface of a biomembrane leading to a comprehensive understanding of the interaction mechanisms involved. At the same time, these experiments show that the Hg-phospholipid model is an effective toxicity sensing technique as shown by the correlation between literature in vivo toxicity data and the data from this study.
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http://dx.doi.org/10.1021/la400923dDOI Listing
June 2013

Interaction of poly(N-isopropylacrylamide) (pNIPAM) based nanoparticles and their linear polymer precursor with phospholipid membrane models.

Bioelectrochemistry 2012 Oct 20;87:211-9. Epub 2011 Dec 20.

New Materials Department, CIDETEC, Donostia-San Sebastian, Spain.

Poly(N-isopropylacrylamide) (pNIPAM) is a thermoresponsive polymer which has promising applications in nanomedicine for drug delivery. The cross-linking of pNIPAM based copolymer using the chain collapse method leads to the synthesis of pNIPAM based polymer nanoparticles. This study looks at the interaction of pNIPAM polymers and pNIPAM nanoparticles with biomembrane models of, (i) a dioleoyl phosphatidylcholine (DOPC) monolayer on a mercury (Hg) electrode and (ii) DOPC and dimyristoyl phosphatidylcholine (DMPC) vesicles. The following techniques were used to follow the interactions: Dynamic light scattering (DLS), differential scanning calorimetry (DSC), rapid cyclic voltammetry (RCV) and electrochemical impedance spectroscopy (EIS). Results showed that the polymers interacted more extensively than the nanoparticles with the phospholipid. The interaction of the polymer was more rapid and led to a polymer-phospholipid conjugate whereas the nanoparticle adsorbed on the phospholipid monolayer surface and penetrated the monolayer at longer contact times. The association of the linear polymer with the phospholipid can be related to the larger molecular area available with the pendant -Cl groups and the inherent polymeric flexibility compared to the nanoparticle structure. The apparent dissociation constant for nanoparticles-DOPC complex was K(d,app)=1.67 × 10(-5)±1.2 × 10(-6) mol dm(-3). The apparent kinetic constant of nanoparticle penetration through the DOPC monolayer was k(2,app)=1.054 × 10(-2)±9.1 × 10(-4) s(-1). It can be concluded therefore that the pNIPAM nanoparticle because of its lower affinity for phospholipids is more appropriate for medical applications.
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http://dx.doi.org/10.1016/j.bioelechem.2011.12.006DOI Listing
October 2012

Electrochemical modeling of the silica nanoparticle-biomembrane interaction.

Langmuir 2012 Jan 22;28(2):1246-55. Epub 2011 Dec 22.

Centre for Molecular Nanoscience (CMNS), School of Chemistry, SPEME, University of Leeds LS2 9JT, UK.

The interaction of amorphous colloidal silica (SiO(2)) nanoparticles of well-defined sizes with a dioleoyl phosphatidylcholine (DOPC) monolayer on a mercury (Hg) film electrode has been investigated. It was shown using electrochemical methods and microcalorimetry that particles interact with the monolayer, and the electrochemical data shows that the extent of interaction is inversely proportional to the particle size. Scanning electron microscopy (SEM) images of the electrode-supported monolayers following exposure to the particles shows that the nanoparticles bind to the DOPC monolayer irrespective of their size, forming a particle monolayer on the DOPC surface. A one-parameter model was developed to describe the electrochemical results where the fitted parameter is an interfacial layer thickness (3.2 nm). The model is based on the adsorptive interactions operating within this interfacial layer that are independent of the solution pH and solution ionic strength. The evidence implies that the most significant forces determining the interactions are van der Waals in character.
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http://dx.doi.org/10.1021/la203568nDOI Listing
January 2012

The preparation of size-controlled functionalized polymeric nanoparticles in micelles.

Nanotechnology 2009 Jul 1;20(29):295605. Epub 2009 Jul 1.

Research Institute of Membrane and Systems Biology, University of Leeds, Leeds LS2 9JT, UK.

The reverse micellar system of dioctyl-sulfosuccinate (AOT)/octane and toluene have been used as a template for polymerization of acrylamide (AA)/bisacrylamide (BAA)-based functionalized polymeric nanoparticles. Such nanoparticles are typically sized between 20 and 90 nm. They can be synthesized with different functional groups according to the monomers added to the polymerization mixture. In our experiments the nanoparticles carried amino and carboxyl groups following incorporation of allylamine (AAm) or methacrylic acid (MAA) monomers, respectively. The available amine or carboxyl groups can then be used for immobilization of enzymes or other biomolecules. These enzymes, subtilisin, laccase and lipase, were immobilized onto polyAA/BAA/MAA nanoparticles covalently after activating the MAA carboxylic groups with Woodward's K reagent. Non-covalent immobilization via electrostatic interaction was also performed.
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http://dx.doi.org/10.1088/0957-4484/20/29/295605DOI Listing
July 2009

Sonochemically fabricated enzyme microelectrode arrays for the environmental monitoring of pesticides.

Biosens Bioelectron 2004 Nov;20(4):765-72

Gwent Electronic Materials, Monmouth House, Mamhilad Park, Pontypool NP4 OHZ, UK.

This paper describes the development of a novel sonochemically fabricated microelectrode based acetylcholinesterase and polyaniline carbon/cobalt phthalocyanine biosensor for the ultra-sensitive determination of pesticides. Arrays of this type are fabricated using microelectrode templates with population densities of 2 x 10(5) cm(-2). The enzymatic response of the sensors is inhibited upon incubation with the pesticide and in this report it is shown that paraoxon may be determined down to concentrations of 1 x 10(-17) M. This sensitivity has thus far not been achieved and mechanisms accounting for the enhancement of the sensitivity reported here are discussed.
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http://dx.doi.org/10.1016/j.bios.2004.06.008DOI Listing
November 2004