John F Callan

University of Ulster, Aontroim, N Ireland, United Kingdom

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Publications (46)199.79 Total impact

  • [Show abstract] [Hide abstract]
    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; · 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; · 3.99 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; · 4.38 Impact Factor
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    ABSTRACT: 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.
    Clinical Oral Investigations 11/2014; · 2.20 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; · 6.38 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). · 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; · 11.44 Impact Factor
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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; · 6.38 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; · 3.91 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.
    Recent Patents on Nanomedicine. 01/2013; 3(2).
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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. · 6.38 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. · 30.43 Impact Factor
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    ABSTRACT: A Rose Bengal sonosensitiser has been covalently attached to a lipid microbubble and the resulting conjugate shown to produce higher levels of singlet oxygen, enhanced cytotoxicity in a cancer cell line and a greater reduction in tumour growth than the sonosensitiser alone.
    Chemical Communications 07/2012; 48(67):8332-4. · 6.38 Impact Factor
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    ABSTRACT: Photodynamic therapy (PDT) is emerging as a treatment modality for the management of neoplastic disease. Despite considerable clinical success, its application for the treatment of deep-seated lesions is constrained by the inability of visible light to penetrate deeply into tissues. An emerging alternative approach exploits the fact that many photosensitisers respond to ultrasound, eliciting cytotoxic effects on target cells and tissues; this has become known as sonodynamic therapy (SDT). The objectives of this study were 1) to determine whether the IR-absorbing dye, indocyanine green (ICG), can be employed as a sonosensitiser and 2) to determine whether ultrasound can be used to enhance ICG-mediated PDT. Exposing ICG-treated mouse fibrosarcoma cells to ultrasound at an energy density of 30 J cm(-2) decreased cell viability by 65 %. Prior exposure of ICG-treated cells to light (λ 830 nm) and subsequent treatment with ultrasound led to a 90 % decrease in cell viability. In combination treatments a synergistic effect was observed at lower doses of ultrasound. Microscopic examination of cell populations treated with light or ultrasound demonstrated the production of intracellular reactive oxygen species (ROS). Using a mouse tumour model, treatment with light, ultrasound, or a combination thereof led to respective decreases in tumour growth of 42, 67, and 98 % at day 27 post-treatment. These results could provide a means of circumventing light-penetration issues that currently challenge the widespread use of PDT in the treatment of cancer.
    ChemMedChem 06/2012; 7(8):1465-71. · 3.05 Impact Factor
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    ABSTRACT: In search of strategies to develop deeply penetrating agents for use in Photodynamic Therapy (PDT), we have devised a Quantum Dot-Rose Bengal conjugate that is effective at producing singlet oxygen upon two-photon irradiation. The CdSe/ZnS Quantum Dot, with its high two photon absorption cross section, serves as a two-photon absorbing antenna and transfers its excited state energy to the attached photosensitiser which engages with molecular oxygen to produce cytotoxic singlet oxygen. Thus, we were able to excite the photosensitiser indirectly, which has an absorption maximum of 565 nm, with two-photon irradiation at 800 nm. Given the tissue penetration depth of 800 nm light is at least four times greater than 565 nm light, this offers the opportunity to access much deeper-seated tumours than is currently possible with pharmaceutically approved photosensitisers. Furthermore, the attachment of the photosensitiser to the hydrophilic quantum dot improved the aqueous solubility of the photosensitiser by 48
    Journal of Materials Chemistry 03/2012; 22(13):6456-6462. · 6.63 Impact Factor
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    ABSTRACT: N-Phenyl-2-(2-hydroxynaphthalen-1-ylmethylene)hydrazinecarbothioamide has been investigated as a fluorescent sensor for the determination of Fe(III) in aqueous solutions. The probe was prepared by the facile Schiff base condensation of 2-hydroxy-1-napthaldehyde with N-phenylhydrazinecarbothioamide. The sensor displayed good selectivity for Fe(III) when tested against a range of biologically and environmentally important cations. A concentration dependent increase in the emission of two fluorescent bands at 425 and 495 nm was observed upon increasing Fe(III) addition resulting in a linear ratiometric response in the 17–37 μM range. The binding stoichiometry was confirmed as 1:1 (host/guest) with the binding constant (log β) calculated as 4.56.
    Tetrahedron Letters 02/2012; 53(6):670–673. · 2.39 Impact Factor
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    ABSTRACT: In search of strategies to photoactivate the luminescence of semiconductor quantum dots, we devised a synthetic approach to attach photocleavable 2-nitrobenzyl groups to CdSe-ZnS core-shell quantum dots coated with hydrophilic polymeric ligands. The emission intensity of the resulting nanostructured constructs increases by more than 60% with the photolysis of the 2-nitrobenzyl appendages. Indeed, the photoinduced separation of the organic chromophores from the inorganic nanoparticles suppresses an electron-transfer pathway from the latter to the former and is mostly responsible for the luminescence enhancement. However, the thiol groups anchoring the polymeric envelope to the ZnS shell also contribute to the photoinduced emission increase. Presumably, their photooxidation eliminates defects on the nanoparticle surface and promotes the radiative deactivation of the excited quantum dots. This effect is fully reversible but its magnitude is only a fraction of the change caused by the photocleavage of the 2-nitrobenzyl groups. In addition, these particular quantum dots can cross the membrane of model cells and their luminescence increases by ~80% after the intracellular photocleavage of the 2-nitrobenzyl quenchers. Thus, photoswitchable luminescent constructs with biocompatible character can be assembled combining the established photochemistry of the 2-nitrobenzyl photocage with the outstanding photophysical properties of semiconductor quantum dots and the hydrophilic character of appropriate polymeric ligands.
    Journal of the American Chemical Society 01/2012; 134(4):2276-83. · 11.44 Impact Factor
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    ABSTRACT: A simple fluorescent sensor 1 has been developed for the recognition of Fe(III) in semi-aqueous solution at pH 7.0. The sensor, containing two Schiff base type receptors directly connected to naphthalene fluorophores, shows a concentration dependent decrease in emission intensity upon Fe(III) addition. The sensor was selective for Fe(III) over other metal ions and can measure Fe(III) ion concentration between 0.05 and 0.12 mM. The binding stoichiometry was established as 1:1 (host: guest) with a binding constant (Logβ) of 4.01. Furthermore, the addition of Fe(III) to a solution of 1 caused a colour change from light yellow to colourless meaning 1 is also capable of detecting Fe(III) by the naked eye.
    Journal of Fluorescence 11/2011; 22(3):795-8. · 1.79 Impact Factor
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    ABSTRACT: A combination of light and ultrasound activation of two conventional photosensitising drugs, methylene blue and rose bengal, was shown to generate higher levels of reactive oxygen species (ROS) and lower LD50 values than either light or ultrasound activation alone.
    Bioorganic & medicinal chemistry letters 08/2011; 21(19):5750-2. · 2.65 Impact Factor
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    ABSTRACT: CdSe/ZnS quantum dots functionalised with [Carboxymethyl-(4-mercapto-phenyl)-amino]-acetate displayed selectivity for Zn 2+ion when tested against a range of other commonly available metal ions in buffered aqueous solution (pH 7.0 ± 0.1). The probe displayed an enhancement in its fluorescence intensity upon addition of Zn2+attributed to a cancellation of a photoinduced electron transfer process from the bound receptor to the excited quantum dot that otherwise led to non-radiative decay. Good linearity was established for Zn2+in the 0.2 to 5.0 mM range.
    International Journal of Biomedical Nanoscience and Nanotechnology. 05/2011; 2(1):3-11.

Publication Stats

800 Citations
199.79 Total Impact Points

Institutions

  • 2010–2014
    • University of Ulster
      • • School of Biomedical Sciences
      • • School of Pharmacy and Pharmaceutical Science
      Aontroim, N Ireland, United Kingdom
  • 2009–2012
    • University of Miami
      • Department of Chemistry
      Coral Gables, FL, United States
  • 2011
    • Universidad de Cádiz
      • Departamento de Química Analítica
      Cadiz, Andalusia, Spain
  • 2008–2009
    • The Robert Gordon University
      • School of Pharmacy and Life Sciences
      Aberdeen, SCT, United Kingdom
  • 2004–2008
    • Queen's University Belfast
      • School of Chemistry and Chemical Engineering
      Béal Feirste, N Ireland, United Kingdom
    • Queen's University
      Kingston, Ontario, Canada