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  • Journal article
    Zeng F, Wu Y, Li X, Ge X, Guo Q, Lou X, Cao Z, Hu B, Long NJ, Mao Y, Li Cet al., 2018,

    Custom-made ceria nanoparticles show a neuroprotective effect by modulating phenotypic polarization of the microglia

    , Angewandte Chemie International Edition, Vol: 57, Pages: 5808-5812, ISSN: 1521-3757

    The neuroprotective effect of ceria nanoparticles in the context of brain disorders has been explained by their antioxidant effect. However, the in-depth mechanism remains unknown. As resident immune cells in the brain, microglia exert a variety of functional reprogramming termed as polarization in response to stress stimuli. Herein, custom-made ceria nanoparticles were developed and found to scavenge multiple reactive oxygen species with extremely high efficiency. These nanoparticles drove microglial polarization from a pro-inflammatory phenotype to an anti-inflammatory phenotype under pathological conditions. Pretreatment of these nanoparticles changed the microglial function from detrimental to protective for the neuronal cells by blocking the pro-inflammatory signaling. This work not only helps to elucidate the mechanism of ceria-nanoparticle-mediated neuroprotection but also provides a new strategy to rebalance the immuno-environment by switching the equilibrium of the phenotypic activation of microglia.

  • Journal article
    Price TW, Firth G, Eling CJ, Kinnon M, Long NJ, Sturge J, Stasiuk GJet al., 2018,

    A F-18 radiolabelled Zn(II) sensing fluorescent probe

    , CHEMICAL COMMUNICATIONS, Vol: 54, Pages: 3227-3230, ISSN: 1359-7345
  • Conference paper
    Bamber J, Shah A, Bush N, Costa M, Harris-Birtill D, Lin S, Singh M, Scienti O, Darabara D, Elson D, ter Haar G, Rivens I, Long N, Tang Met al., 2018,

    Photoacoustic imaging and contrast agents in cancer research

    , Leeds Microbubble Symposium
  • Conference paper
    Leow CH, Marta B, Stanziola A, Hernandez-Gil J, Long NJ, Aboagye EO, Tang M-Xet al., 2017,

    Multi-Frame Rate Plane Wave Contrast-Enhance Ultrasound Imaging for Tumour Vasculature Imaging and Perfusion Quantification

    , IEEE International Ultrasonics Symposium (IUS), Publisher: IEEE, ISSN: 1948-5719

    A multi-frame rate plane wave imaging strategy is developed to simultaneously image tumor vasculature and quantify tumor perfusion. Customised imaging sequences interleaving a short but high frame rate (HFR) plane wave imaging sequence with a long but low frame rate imaging (LFR) sequence were implemented using a programmable ultrasound research platform. The results from a spatio-temporal coherence processing technique of ours demonstrated a significant improvement in the SNR and vasculature contrast when compared with the existing ultrafast Power Doppler (PD) using the same data. Initial perfusion quantification using LFR imaging was also demonstrated. Mean time intensity curve and some parametric measures were generated. Combining both structural and functional perfusion imaging using the multiframe rate sequences, a better evaluation of the tumour angiogenesis can be assessed.

  • Conference paper
    Morse SV, Pouliopoulos AN, Chan T, Lin J, Copping M, Long NJ, Choi JJet al., 2017,

    Rapid short-pulse (RaSP) sequences improve the distribution of drug delivery to the brain in vivo

    , IEEE UFFC, Publisher: IEEE, ISSN: 1948-5719

    Focused ultrasound and microbubbles have been shown to locally and noninvasively open the blood-brain barrier. Despite encouraging results in human patients, several performance and safety features, such as poor drug distribution, high drug accumulation along vessels and small sites of red blood cell extravasation, have been unavoidable. We have recently developed a new ultrasound sequence - rapid short-pulse (RaSP) sequence - designed to suppress these adverse features by promoting safer modes of cavitation activity throughout capillaries. In our RaSP sequences, low-pressure short ultrasonic pulses are emitted at kHz pulse repetition frequencies (PRF) and grouped into bursts. We have shown in vitro that RaSP sequences prolong microbubble lifetime and increase their mobility, enhancing the distribution of acoustic cavitation activity. Here we evaluate the ability of RaSP sequences to improve the in vivo performance and safety of ultrasound-mediated drug delivery to the brain.

  • Conference paper
    Leow CH, Braga M, Hernandez-Gil J, Long NJ, Aboagye EO, Tang MXet al., 2017,

    Multi-frame rate plane wave contrast-enhanced ultrasound imaging for tumour vascular imaging and perfusion quantification

    , IEEE International Ultrasonics Symposium, IUS, Publisher: IEEE, ISSN: 1948-5719

    Angiogenesis and blood flow dynamics play an important role in the development of malignant tumours and their response to treatment. While contrast enhanced ultrasound (CEUS) imaging with microbubble contrast agents as a tool for imaging angiogenesis and flow dynamics has shown great potential [1], recent development of plane wave high frame-rate (HFR) CEUS has offered new opportunities in such applications. In this study, we demonstrate an interleaved multi-frame rate plane wave CEUS imaging to quantify perfusion and to image vascular structure with improved resolution and contrast.

  • Conference paper
    Lin S, Shah A, Hernandez-Gil J, Stanziola A, Harriss B, Matsunaga T, Long N, Bamber J, Tang MXet al., 2017,

    Notice of Removal: Optically and acoustically triggerable sub-micron phase-change contrast agents for enhanced photoacoustic and ultrasound imaging

    , ISSN: 1948-5719

    To explore the extravascular space, sub-micron phase-change droplets show widespread interest in medical imaging and therapy with various modalities, such as ultrasound and photoacoustic. Existing studies (Wilson 2012, Wei 2014) on such dual-modality contrast agents have demonstrated the generation of both optical and ultrasound contrast after optical activation. However these studies did not explore the option of acoustic activation. Furthermore, high boiling point perfluorocarbons were used in these studies. A low boiling point may be preferred, to minimise un-wanted bioeffects, especially when activating in deeper tissues. In this study, we demonstrate a versatile phase-change sub-micron contrast agent that can provide three modes of contrast enhancement: 1) photoacoustic imaging contrast, 2) ultrasound contrast with optical activation, and 3) ultrasound contrast with acoustic activation. This would add versatility of vaporisation triggering, offering new possibilities in dual mode imaging, molecular imaging and drug delivery.

  • Journal article
    Du S, Hernandez-Gil J, Dong H, Zheng X, Lyu G, Banobre-Lopez M, Gallo J, Sun L-D, Yan C-H, Long NJet al., 2017,

    Design and validation of a new ratiometric intracellular pH imaging probe using lanthanide-doped upconverting nanoparticles

    , Dalton Transactions, Vol: 46, Pages: 13957-13965, ISSN: 1477-9234

    pH homeostasis is strictly controlled at a subcellular level. A deregulation of the intra/extra/subcellular pH environment is associated with a number of diseases and as such, the monitoring of the pH state of cells and tissues is a valuable diagnostic tool. To date, only a few tools have been developed to measure the pH in living cells with the spatial resolution needed for intracellular imaging. Among the techniques available, only optical imaging offers enough resolution and biocompatibility to be proposed for subcellular pH monitoring. We present herein a ratiometric probe based on upconversion nanoparticles modified with a pH sensitive moiety for the quantitative imaging of pH at the subcellular level in living cells. This system provides the properties required for live cell quantitative imaging i.e. positive cellular uptake, biocompatibility, long wavelength excitation, sensitive response to pH within a biologically relevant range, and self-referenced signal.

  • Journal article
    Parker D, Long NJ, Faulkner S, 2017,

    Challenges for chemistry in molecular imaging

    , Philosophical Transactions of the Royal Society A. Mathematical, Physical and Engineering Sciences, Vol: 375, ISSN: 1364-503X
  • Journal article
    Leber R, Wilson LE, Robaschik P, Inkpen MS, Payne DJ, Long NJ, Albrecht T, Hirjibehedin CF, Heutz Set al., 2017,

    High Vacuum Deposition of Biferrocene Thin Films on Room Temperature Substrates

    , Chemistry of Materials, Vol: 29, Pages: 8663-8669, ISSN: 0897-4756

    Metallocenes are a promising candidate for future spintronic devices due to their versatile and tunable magnetic properties. However, single metallocenes, e.g., ferrocene, sublimate below room temperature, and therefore the implementation for future applications is challenging. Here, a method to prepare biferrocene thin films using organic molecular beam deposition (OMBD) is presented, and the effect of substrate and deposition rate on the film structure and morphology as well as its chemical and magnetic properties is investigated. On Kapton and Si substrates, biferrocene interacts only weakly with the substrate, and distinct grains scattered over the surface are observed. By incorporating a 3,4,9,10-perylenetetracarboxylic dianhydride (PTCDA) seeding layer and depositing biferrocene at high deposition rates of 1.0 Å s–1, it is possible to achieve a well-ordered densely packed film. With spintronic applications in mind, the magnetic properties of the thin films are characterized using superconducting quantum interference device (SQUID) magnetometry. Whereas initial SQUID measurements show weak ferromagnetic behavior up to room temperature due to oxidized molecule fragments, measurements of biferrocene on PTCDA capped with LiF show the diamagnetic behavior expected of biferrocene. Through the successful deposition of biferrocene thin films and the ability to control the spin state, these results demonstrate a first step toward metallocene-based spintronics.

  • Conference paper
    Zhang G, Lin S, Leow CH, Pang K, Hernandez-Gil J, Chee M, Long NJ, Matsunaga TO, Tang M-Xet al., 2017,

    Acoustic Response of Targeted Nanodroplets Post-Activation using High Frame Rate Imaging

    , IEEE International Ultrasonics Symposium (IUS), Publisher: IEEE, ISSN: 1948-5719
  • Journal article
    Gallo J, Harriss BI, Hernandez-Gil J, Banobre-Lopez M, Long NJet al., 2017,

    Probing T-1-T-2 interactions and their imaging implications through a thermally responsive nanoprobe

    , Nanoscale, Vol: 9, Pages: 11318-11326, ISSN: 2040-3364

    The complex and specialised diagnostic process through magnetic resonance imaging (MRI) could be simplified with the implementation of dual T1–T2 contrast agents. T1- and T2-weighted MR are compatible modalities, and co-acquisition of contrast enhanced images in both T1 and T2 will drastically reduce artefacts and provide double-checked results. To date, efforts in the development of dual MRI probes have provided inconsistent results. Here we present the preparation and relaxometric study of a dual T1–T2 MRI probe based on superparamagnetic nanoparticles, paramagnetic Gd3+ chelates and pNIPAM (poly(N-isopropylacrylamide)), in which the distance between paramagnetic and superparamagnetic species can be modulated externally via temperature variations. Such a probe alleviates traditional nanotechnology limitations (e.g. batch to batch variability) as comparisons can be established within a single probe.

  • Journal article
    Al-Owaedi OA, Bock S, Milan DC, Oerthel M-C, Inkpen MS, Yufit DS, Sobolev AN, Long NJ, Albrecht T, Higgins SJ, Bryce MR, Nichols RJ, Lambert CJ, Low PJet al., 2017,

    Insulated molecular wires: inhibiting orthogonal contacts in metal complex based molecular junctions

    , Nanoscale, Vol: 9, Pages: 9902-9912, ISSN: 2040-3364

    Metal complexes are receiving increased attention as molecular wires in fundamental studies of the transport properties of metal|molecule|metal junctions. In this context we report the single-molecule conductance of a systematic series of d8 square-planar platinum(II) trans-bis(alkynyl) complexes with terminal trimethylsilylethynyl (C[triple bond, length as m-dash]CSiMe3) contacting groups, e.g. trans-Pt{C[triple bond, length as m-dash]CC6H4C[triple bond, length as m-dash]CSiMe3}2(PR3)2 (R = Ph or Et), using a combination of scanning tunneling microscopy (STM) experiments in solution and theoretical calculations using density functional theory and non-equilibrium Green's function formalism. The measured conductance values of the complexes (ca. 3–5 × 10−5G0) are commensurate with similarly structured all-organic oligo(phenylene ethynylene) and oligo(yne) compounds. Based on conductance and break-off distance data, we demonstrate that a PPh3 supporting ligand in the platinum complexes can provide an alternative contact point for the STM tip in the molecular junctions, orthogonal to the terminal C[triple bond, length as m-dash]CSiMe3 group. The attachment of hexyloxy side chains to the diethynylbenzene ligands, e.g. trans-Pt{C[triple bond, length as m-dash]CC6H2(Ohex)2C[triple bond, length as m-dash]CSiMe3}2(PPh3)2 (Ohex = OC6H13), hinders contact of the STM tip to the PPh3 groups and effectively insulates the molecule, allowing the conductance through the full length of the backbone to be reliably measured. The use of trialkylphosphine (PEt3), rather than triarylphosphine (PPh3), ancillary ligands at platinum also eliminates these orthogonal contacts. These results have significant implications for the future design of organometallic complexes for studies in molecular junctions.

  • Journal article
    Wilson LE, Hassenrück C, Winter RF, White AJP, Albrecht T, Long NJet al., 2017,

    Ferrocene‐ and Biferrocene‐Containing Macrocycles towards Single‐Molecule Electronics

    , Angewandte Chemie, Vol: 129, Pages: 6942-6946, ISSN: 0044-8249

    <jats:title>Abstract</jats:title><jats:p>Cyclic multiredox centered systems are currently of great interest, with new compounds being reported and developments made in understanding their behavior. Efficient, elegant, and high‐yielding (for macrocyclic species) synthetic routes to two novel alkynyl‐conjugated multiple ferrocene‐ and biferrocene‐containing cyclic compounds are presented. The electronic interactions between the individual ferrocene units have been investigated through electrochemistry, spectroelectrochemistry, density functional theory (DFT), and crystallography to understand the effect of cyclization on the electronic properties and structure.</jats:p>

  • Journal article
    Long NJ, albrecht T, wilson L, white A, winter R, hassenruck Cet al., 2017,

    Ferrocene- and biferrocene-containing macrocycles towards single molecule electronics

    , Angewandte Chemie-International Edition, Vol: 56, Pages: 6838-6824, ISSN: 1521-3773

    Cyclic multiredox centered systems are currently of great interest, with new compounds being reported and developments made in understanding their behavior. Efficient, elegant, and high-yielding (for macrocyclic species) synthetic routes to two novel alkynyl-conjugated multiple ferrocene- and biferrocene-containing cyclic compounds are presented. The electronic interactions between the individual ferrocene units have been investigated through electrochemistry, spectroelectrochemistry, density functional theory (DFT), and crystallography to understand the effect of cyclization on the electronic properties and structure.

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