[Show abstract][Hide abstract] ABSTRACT: The interest in Quantum Dots as a class of nanomaterials has grown considerably since their discovery by Ekimov and Efros in the early 1980s. Although this early work focussed primarily on CdSe-based nanocrystals, the field has now expanded to include various classes of nanoparticles with different types of core, shell or passivation chemistry. Such differences can have a profound effect on the optical properties and potential biocompatibility of the resulting constructs. Although QDs have predominantly been used for imaging and sensing applications, more examples of their use as therapeutics are beginning to emerge. In this chapter we discuss the progress made over the past decade in developing QDs for imaging and therapeutic applications.
Topics in current chemistry 11/2015; 370:203-224. DOI:10.1007/978-3-319-22942-3_7 · 4.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A new sensitiser (4) for use in photodynamic therapy (PDT) has been developed to enable control ROS production as a function of pH. This pH dependent PDT behaviour was tested in HeLa cells and in SCID mice bearing human xenograft pancreatic cancer (BxPC-3) tumours.
Chemical Communications 09/2015; 51(94). DOI:10.1039/C5CC07022H · 6.83 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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 · 33.38 Impact Factor
[Show abstract][Hide abstract] 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 · 3.09 Impact Factor
[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; 31(2). DOI:10.3109/02656736.2014.992484 · 2.65 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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.
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.
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.
Carbamide Plus offers the potential of using significantly lower levels of hydrogen peroxide concentration to achieve similar dental whitening effects.
[Show abstract][Hide abstract] 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
[Show abstract][Hide abstract] 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 · 3.09 Impact Factor
[Show abstract][Hide abstract] 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 · 12.11 Impact Factor