John F Callan

University of Ulster, Aontroim, Northern Ireland, United Kingdom

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Publications (55)263.21 Total impact

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    ABSTRACT: A strategy to probe supramolecular nanocarriers and their cargo in the intracellular space was developed on the basis of fluorescence measurements and energy transfer. It relies on the covalent attachment of an energy donor, or acceptor, to the macromolecular backbone of amphiphilic polymers and the noncovalent encapsulation of a complementary acceptor, or donor, in the resulting micelles. In aqueous environments, these macromolecules self-assemble into nanostructured constructs and bring the complementary chromophores in close proximity to enable efficient energy transfer. These supramolecular assemblies travel from the extracellular to the intracellular space and retain their integrity in the process. Indeed, donors and acceptors remain close to each other after internalization and excitation of the former chromophores translates into significant intracellular emission from the latter. Furthermore, these supramolecular assemblies exchange their components with fast kinetics in aqueous dispersions, because of the reversible character of the noncovalent contacts holding them together. As a result, micelles incorporating exclusively the donors and nanocarriers containing only the acceptors scramble their chromophoric building blocks, upon mixing, to allow the transfer of energy. These dynamic processes can be reproduced in the intracellular environment with the sequential incubation of cells with the two sets of complementary nanostructured assemblies. Thus, these operating principles and choice of supramolecular synthons are particularly valuable to monitor self-assembling nanocarriers and their cargo inside living cells and can facilitate the elucidation of the behavior of these promising delivery vehicles in a diversity of biological specimens.
    Langmuir 08/2015; DOI:10.1021/acs.langmuir.5b01949 · 4.46 Impact Factor
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    ABSTRACT: An amphiphilic polymer with multiple decyl and oligo(ethylene glycol) chains attached to a common poly(methacrylate) backbone assembles into nanoscaled particles in aqueous environments. Hydrophobic anthracene and borondipyrromethene (BODIPY) chromophores can be co-encapsulated within the self-assembling nanoparticles and transported across hydrophilic media. The reversible character of the noncovalent bonds, holding the supramolecular containers together, permits the exchange of their components with fast kinetics in aqueous solution. Incubation of cells with a mixture of two sets of nanoparticles, pre-loaded independently with anthracene or BODIPY chromophores, results in guest scrambling first and then transport of co-entrapped species to the intracellular space. Alternatively, incubation of cells with the two sets of nanocarriers in consecutive steps permits the sequential transport of the anthracene and BODIPY chromophores across the plasma membrane and only then allows their co-encapsulation within the same supramolecular containers. Both mechanisms position the two sets of chromophores with complementary spectral overlap in close proximity to enable the efficient transfer of energy intracellularly from the anthracene donors to the BODIPY acceptors. In the presence of iodine substituents on the BODIPY platform, intersystem crossing follows energy transfer. The resulting triplet state can transfer energy further to molecular oxygen with the concomitant production of singlet oxygen to induce cell mortality. Furthermore, the donor can be excited with two near-infrared photons simultaneously to permit the photoinduced generation of singlet oxygen intracellularly under illumination conditions compatible with applications in vivo. Thus, these supramolecular strategies to control the excitation dynamics of multichromophoric assemblies in the intracellular environment can evolve into valuable protocols for photodynamic therapy.
    Nanoscale 07/2015; DOI:10.1039/C5NR02672E · 7.39 Impact Factor
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    ABSTRACT: A new anion selective chemosensor L was derived through a direct condensation reaction between pyridoxal and thiosemicarbazide. Sensor L showed selective recognition and sensing ability towards F- and AcO- anions through naked-eye detectable color change from colorless to light yellow, appearance of a new charge transfer absorption band at 404 nm and significant “turn-on” fluorescence at 506 nm. The detection limit of L as a fluorescent ‘turn-on’ sensor for the analysis of F- and AcO- was estimated to be 0.10 M. The anion sensing mechanisms of L was supported with 1H NMR and DFT results. Finally, the cytoxicity effect of L and its ability to image intracellular F- ions in the living HeLa cells was investigated.
    RSC Advances 06/2015; 5(63). DOI:10.1039/C5RA05059F · 3.84 Impact Factor
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    ABSTRACT: Luminescent sensors and switches continue to play a key role in shaping our understanding of key biochemical processes, assist in the diagnosis of disease and contribute to the design of new drugs and therapies. Similarly, their contribution to the environment cannot be understated as they offer a portable means to undertake field testing for hazardous chemicals and pollutants such as heavy metals. From a physiological perspective, the Group I and II metal ions are among the most important in the periodic table with blood plasma levels of H(+), Na(+) and Ca(2+) being indicators of several possible disease states. In this review, we examine the progress that has been made in the development of luminescent probes for Group I and Group II ions as well as protons. The potential applications of these probes and the mechanism involved in controlling their luminescent response upon analyte binding will also be discussed.
    Chemical Society Reviews 03/2015; 44(13). DOI:10.1039/c4cs00365a · 30.43 Impact Factor
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    ABSTRACT: A polymeric hydrogel containing a photoinduced electron transfer (PET) based probe for Zn(II) has been formulated into the wells of a 96-well plate. Upon addition of Zn(II) ions to selected wells, the fluorescence of the gel was observed to increase in a concentration dependent manner in the 0.25 – 1.75 mM range. The millimolar binding constant observed for this probe is higher than that reported for other Zn(II) probes in the literature and offers the possibility to determine the concentration of this ion in environments where the Zn(II) concentration is high. The combination of the multi-well plate set-up with fluorescence detection offers the possibility of high-throughput screening of Zn(II) using low sample volumes in a timely manner. To the best of our knowledge, this is the first reported example of a polymeric hydrogel sensor for zinc with capability for use in fluorescence multi-well plate assay.
    New Journal of Chemistry 02/2015; 39(5). DOI:10.1039/C5NJ00259A · 3.16 Impact Factor
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    ABSTRACT: Tumour hypoxia represents a major challenge in the effective treatment of solid cancerous tumours using conventional approaches. As oxygen is a key substrate for Photo-/Sono-dynamic Therapy (PDT/SDT), hypoxia is also problematic for the treatment of solid tumours using these techniques. The ability to deliver oxygen to the vicinity of the tumour increases its local partial pressure improving the possibility of ROS generation in PDT/SDT. In this manuscript, we investigate the use of oxygen-loaded, lipid-stabilised microbubbles (MBs), decorated with a Rose Bengal sensitiser, for SDT-based treatment of a pancreatic cancer model (BxPc-3) in vitro and in vivo. We directly compare the effectiveness of the oxygen-loaded MBs with sulphur hexafluoride (SF6)-loaded MBs and reveal a significant improvement in therapeutic efficacy. The combination of oxygen-carrying, ultrasound-responsive MBs, with an ultrasound-responsive therapeutic sensitiser, offers the possibility of delivering and activating the MB-sensitiser conjugate at the tumour site in a non-invasive manner, providing enhanced sonodynamic activation at that site. Copyright © 2015. Published by Elsevier B.V.
    Journal of Controlled Release 02/2015; 203. DOI:10.1016/j.jconrel.2015.02.004 · 7.26 Impact Factor
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    ABSTRACT: Sonodynamic therapy (SDT) has emerged as a promising option for the minimally invasive treatment of solid cancerous tumours. SDT requires the combination of three distinct components: a sensitising drug, ultrasound, and molecular oxygen. Individually, these components are non-toxic but when combined together generate cytotoxic reactive oxygen species (ROS). The major advantage of SDT over its close relative photodynamic therapy (PDT), is the increased penetration of ultrasound through mammalian tissue compared to light. As a result, SDT can be used to treat a wider array of deeper and less accessible tumours than PDT. In this article, we critically review the current literature on SDT and discuss strategies that have been developed in combination with SDT to enhance the therapeutic outcome.
    International Journal of Hyperthermia 01/2015; 31(2). DOI:10.3109/02656736.2014.992484 · 2.77 Impact Factor
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    ABSTRACT: The field of therapeutics is evolving to include a greater proportion of higher molecular weight, hydrophilic biological compounds. To cater for this new era in healthcare the concomitant development of appropriate drug delivery systems is essential to aid cellular permeation. In this manuscript we present the synthesis, characterisation and biological evaluation of a charge neutral polymersome (Ps) based drug delivery system (DDS) using an amphiphilic pegylated random copolymer. A detailed dynamic light scattering study revealed that the hydrodynamic diameter of the Ps can be tailored to a specific size simply by varying the quantities and ratios used during the preparation step. The zeta potential of this new drug delivery system was determined to be -0.095±0.037mV, the encapsulation efficiency of FITC-CM-dextran (4KDa) was 70%, the uptake of Fitc-CM-Dextran by Hela cells was increased 4-fold when encapsulated within the polymersomal system. The facile preparation, high loading capacity and size tuneable nature of this Ps renders it a promising alternative to the ever growing array of currently available Ps. Copyright © 2015 Elsevier B.V. All rights reserved.
    International Journal of Pharmaceutics 01/2015; 481(1-2). DOI:10.1016/j.ijpharm.2014.12.061 · 3.65 Impact Factor
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    ABSTRACT: Microbubbles (MBs) have recently emerged as promising delivery vehicles for sensitiser drugs in sonodynamic therapy (SDT). The ability to selectively destroy the MB and activate the sensitizer using an external ultrasound trigger could provide a minimally invasive and highly targeted therapy. While lipid MBs have been approved for use as contrast agents in diagnostic ultrasound, the attachment of sensitiser drugs to their surface results in a significant reduction in particle stability. In this manuscript, we prepare both lipid and polymer (PLGA) MBs with rose bengal attached to their surface and demonstrate that PLGA MB conjugates are significantly more stable than their lipid counterparts. In addition, the improved stability offered by the PLGA shell does not hinder their selective destruction using therapeutically acceptable ultrasound intensities. Furthermore, we demonstrate that treatment of ectopic human tumours (BxPC-3) in mice with the PLGA MB-rose bengal conjugate and ultrasound reduced tumour volume by 34% 4 days after treatment while tumours treated with the conjugate alone increased in volume by 48% over the same time period. Therefore, PLGA MBs may offer a more stable alternative to lipid MBs for the site specific delivery of sensitisers in SDT.
    Langmuir 11/2014; DOI:10.1021/la503929c · 4.46 Impact Factor
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    ABSTRACT: Objectives This study aimed to develop and characterise a new three-component dental whitening formulation which is as effective as the currently used carbamide peroxide but at significantly lower hydrogen peroxide concentrations. Materials and methods The new formulation (Carbamide Plus) was prepared containing hydrogen peroxide, urea, and sodium tripolyphosphate and compared directly with carbamide peroxide (containing just hydrogen peroxide and urea). To evaluate the clinical effectiveness of 5 % Carbamide Plus, a randomised double-blind placebo-controlled clinical trial was conducted comparing the tooth colour of 33 patients using L*a*b* scores at baseline and after a 2-week whitening treatment. The behaviour of the three components in solution was determined by 1H and 31P NMR spectroscopy and pH dilution experiments. Results This clinical trial revealed that 5 % whitening gels containing Carbamide Plus were as effective as those containing 10 % carbamide peroxide. 1H and 31P NMR spectroscopy revealed strong intermolecular interactions between hydrogen peroxide and both urea and sodium tripolyphosphate (STPP) with little apparent interaction between urea and STPP. Conclusions In this manuscript, we postulate that this increased whitening efficiency is due to a marked increase in local pH upon dilution which destabilises the hydrogen peroxide and expedites the whitening process. We postulate Carbamide Plus to be a three-component adduct with two molecules of carbamide peroxide binding to a central STPP unit with no direct interaction between STPP and urea. There were no statistically significant differences between Carbamide Plus and 10 % carbamide peroxide in tooth-whitening achieved at 2 weeks. These results were recorded following 2 weeks of 2-h daily wear of at-home trays. Clinical relevance Carbamide Plus offers the potential of using significantly lower levels of hydrogen peroxide concentration to achieve similar dental whitening effects.
    Clinical Oral Investigations 11/2014; DOI:10.1007/s00784-014-1352-9 · 2.29 Impact Factor
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    ABSTRACT: We report a conjugate between carbon quantum dots and a NO photoreleaser able to photogenerate the anticancer NO radical via an energy transfer mechanism. This nanohybrid proved toxic to cancer cells in vitro and significantly reduced tumor volume in mice bearing human xenograft BxPC-3 pancreatic tumors upon two-photon excitation with the highly biocompatible 800 nm light.
    Chemical Communications 11/2014; 51(1). DOI:10.1039/C4CC07827F · 6.83 Impact Factor
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    ABSTRACT: A polymeric ratiometric fluorescent sensor for Zn(II) has been developed based on a Zn(II) responsive naphthalimide fluorophore (λEM 535 nm) and a Zn(II) insensitive rhodamine calibration fluorophore (λEM 579 nm) both coupled to a common poly(allyl amine) backbone. A concentration dependent increase in the ratiometric response (I535 nm/I579 nm) was observed in the 0–25 mM Zn(II) ion range for the sensor in aqueous buffer. The effect of dilution on the ratiometric intensity of the polymeric sensor was also studied and no change in ratiometric response was observed upon dilution to 50% of its original concentration. In contrast, when the polymeric sensor was incorporated within a Gantrez AN-139 hydrogel matrix, a linear ratiometric response was observed upon addition of increasing amounts of Zn(II) to the gel. Therefore, this approach offers the opportunity to determine Zn(II) concentration in environments where sensor concentration may vary dramatically.
    New Journal of Chemistry 06/2014; 38(7). DOI:10.1039/C4NJ00291A · 3.16 Impact Factor
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    ABSTRACT: Decyl and oligo(ethylene glycol) chains were appended to the same poly(methacrylate) backbone to generate an amphiphilic polymer with a ratio between hydrophobic and hydrophilic segments of 2.5. At concentrations greater than 10 g mL-1 in neutral buffer, multiple copies of this particular macromolecule assemble into nanoparticles with hydrodynamic diameter of 15 nm. In the process of assembling, these nanoparticles can capture anthracene donors and borondipyrromethene acceptors within their hydrophobic interior and permit the transfer of excitation energy with an efficiency of 95%. Energy transfer is observed also if nanocarriers containing exclusively the donors are mixed with nanoparticles pre-loaded separately with the acceptors in aqueous media. The two sets of supramolecular assemblies exchange their guests with fast kinetics upon mixing to co-localize complementary chromophores within the same nanostructured container and enable energy transfer. After guest exchange, the nanoparticles can cross the membrane of cervical cancer cells and bring the co-entrapped donors and acceptors within the intracellular environment. Alternatively, intracellular energy transfer is also established after sequential cell incubation with nanoparticles containing the donors first and then with nanocarriers pre-loaded with the acceptors or vice versa. Under these conditions, the nanoparticles exchange their cargo only after internalization and allow energy transfer exclusively within the cell interior. Thus, the dynamic character of such supramolecular containers offers the opportunity to transport independently complementary species inside cells and permit their interaction only within the intracellular space.
    Journal of the American Chemical Society 05/2014; 136(22). DOI:10.1021/ja500285p · 11.44 Impact Factor
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    ABSTRACT: A novel nanosensing system was developed by the surface functionalization of silver nanoparticles (AgNPs) with β-alanine dithiocarbamate (ADTC) for the selective recognition and monitoring of Hg2+ and Fe3+ ions in aqueous medium. This system showed a visually detectable colour change from yellow to colourless and the surface plasmon resonance (SPR) band of AgNPs at 402 nm disappeared with the addition of both Hg2+ and Fe3+ ions due to the aggregation of nanoparticles. Interestingly, the functionalized AgNPs can be applied for the discrimination and selective detection of Hg2+ and Fe3+ in the presence of Br− and Cl−, respectively.
    RSC Advances 01/2014; 4(3):1341. DOI:10.1039/c3ra44945a · 3.84 Impact Factor
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    ABSTRACT: Luminescent sensors and switches continue to play a Q3 key role in shaping our understanding of key biochemical processes, assist in the diagnosis of disease and contribute to the design of new drugs and therapies. Please check this proof carefully. Our staff will not read it in detail after you have returned it. Translation errors between word-processor files and typesetting systems can occur so the whole proof needs to be read. Please pay particular attention to: tabulated material; equations; numerical data; figures and graphics; and references. If you have not already indicated the corresponding author(s) please mark their name(s) with an asterisk. Please e-mail a list of corrections or the PDF with electronic notes attached – do not change the text within the PDF file or send a revised manuscript. Corrections at this stage should be minor and not involve extensive changes. All corrections must be sent at the same time. Please bear in mind that minor layout improvements, e.g. in line breaking, table widths and graphic placement, are routinely applied to the final version. Please note that, in the typefaces we use, an italic vee looks like this: n, and a Greek nu looks like this: n. We will publish articles on the web as soon as possible after receiving your corrections; no late corrections will be made. Please return your final corrections, where possible within 48 hours of receipt, by e-mail to: chemsocrev@rsc.org
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    ABSTRACT: A carbon quantum dot (CQD)-protoporphyrin (IX) sensitisier conjugate was designed to exploit the large two-photon absorption cross section of CQDs and enable the indirect excitation of the sensitiser with 800 nm irradiation via FRET.
    Chemical Communications 08/2013; 49(79). DOI:10.1039/c3cc45181j · 6.83 Impact Factor
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    ABSTRACT: A novel vitamin B6 Schiff base analog () was synthesized by combining vitamin B6 cofactor pyridoxal with 2-aminophenol. Receptor displays a color change detectable by the naked-eye from yellow to red in the presence of fluoride and acetate due to the formation of hydrogen bonding host-guest complexes in 1 : 1 stoichiometry. Importantly, receptor showed fluoride-selective 'turn-on' fluorescent response with a detection limit (3σ) of 7.39 × 10(-8) M.
    The Analyst 05/2013; 138(13). DOI:10.1039/c3an00199g · 4.11 Impact Factor
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    ABSTRACT: Nanotechnology has the potential to have a revolutionary impact on targeted cancer diagnosis and therapy. A major challenge in cancer diagnosis is to be able to non-invasively detect tumors at an early stage for maximum therapeutic benefit. In the development of effective therapeutic approaches, targeting and localized delivery are the key challenges. However, because many anticancer drugs are designed to simply kill cancer cells, often in a semi-specific fashion, the distribution of anticancer drugs in healthy cells and tissues is especially undesirable due to the potential for severe side effects. This review will address the state of the art in nanotechnologies, and their ongoing applications focused on addressing the challenges posed by the early detection and targeted treatment of cancer. Some relevant patents have also been discussed.
    01/2013; 3(2). DOI:10.2174/1877912304999140203115528
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    ABSTRACT: Highly luminescent, water-soluble and biocompatible Carbon Quantum Dots (aqCQDs) were prepared by encapsulating the parent hydrophobic CQDs in an amphiphilic polymer. The resulting aqCQDs were non-toxic to living cells, and were found to cross the cell membrane and localise primarily in the cytosol.
    Chemical Communications 08/2012; 48(75):9361-3. DOI:10.1039/c2cc34962k · 6.83 Impact Factor
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    ABSTRACT: Iron is one of the most important elements in metabolic processes, being indispensable for all living systems and therefore it is extensively distributed in environmental and biological materials. However, both its deficiency and excess from the normal permissible limit can induce serious disorders. Therefore, several analytical techniques have been adopted for the detection of iron. Among the various techniques used for its detection, the method based on fluorescent sensors has received considerable interest in recent years because of its ability to provide online monitoring of very low concentrations without any pre-treatment of the sample together with the advantages of spatial and temporal resolution. In this article, efforts have been made to review the various molecular and supramolecular fluorescent sensors that have been developed for the selective detection of iron(iii).
    Chemical Society Reviews 08/2012; 41(21):7195-227. DOI:10.1039/c2cs35152h · 30.43 Impact Factor

Publication Stats

2k Citations
263.21 Total Impact Points

Institutions

  • 2010–2015
    • University of Ulster
      • • Biomedical Sciences Research Institute
      • • School of Biomedical Sciences
      • • School of Pharmacy and Pharmaceutical Science
      Aontroim, Northern Ireland, United Kingdom
  • 2007–2009
    • The Robert Gordon University
      • School of Pharmacy and Life Sciences
      Aberdeen, Scotland, United Kingdom
  • 2004–2008
    • Queen's University Belfast
      • School of Chemistry and Chemical Engineering
      Béal Feirste, Northern Ireland, United Kingdom