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Journal articleMcCluskey S, Haslop A, Coello C, et al., 2019,
Imaging chemotherapy induced acute cardiotoxicity with 18F-labelled lipophilic cations
, Journal of Nuclear Medicine, Vol: 60, Pages: 1750-1756, ISSN: 1535-5667Many chemotherapy agents are toxic to the heart, such that increasing numbers of cancer survivors are now living with the potentially lethal cardiovascular consequences of their treatment. Earlier and more sensitive detection of chemotherapy-induced cardiotoxicity may allow improved treatment strategies and increase long-term survival. Lipophilic cation positron emission tomography (PET) tracers may be suitable for early detection of cardiotoxicity. This study aims to evaluate an 18F-labelled lipophilic phosphonium cation e.g. 18F-Mitophos, as a cardiac imaging agent, comparing it to leading PET and SPECT lipophilic cationic tracers before further assessing its potential for imaging cardiotoxicity in an acute doxorubicin (DOX) model.
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Journal articleBoltersdorf T, Ansari J, Senchenkova EY, et al., 2019,
Development, characterisation and in vitro evaluation of lanthanide-based FPR2/ALX-targeted imaging probes.
, Dalton Trans, Vol: 48, Pages: 16764-16775We report the design, preparation and characterisation of three small-molecule, Formyl Peptide Receptor (FPR)-targeted lanthanide complexes (Tb·14, Eu·14 and Gd·14). Long-lived, metal-based emission was observed from the terbium complex (τH2O = 1.9 ms), whereas only negligible lanthanide signals were detected in the europium analogue. Ligand-centred emission was investigated using Gd·14 at room temperature and 77 K, leading to the postulation that metal emission may be sensitised via a ligand-based charge transfer state of the targeting Quin C1 unit. Comparatively high longitudinal relaxivity values (r1) for octadentate metal complexes of Gd·14 were determined (6.9 mM-1 s-1 at 400 MHz and 294 K), which could be a result of a relative increase in twisted square antiprism (TSAP) isomer prevalence compared to typical DOTA constructs (as evidenced by NMR spectroscopy). In vitro validation of concentration responses of Tb·14via three key neutrophil functional assays demonstrated that the inflammatory responses of neutrophils (i.e. chemotaxis, transmigration and granular release) remained unchanged in the presence of specific concentrations of the compound. Using a time-resolved microscopy set-up we were able to observe binding of the Tb·14 probe to stimulated human neutrophils around the cell periphery, while in the same experiment with un-activated neutrophils, no metal-based signals were detected. Our results demonstrate the utility of Tb·14 for time-resolved microscopy with lifetimes several orders of magnitude longer than autofluorescent signals and a preferential uptake in stimulated neutrophils.
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Journal articleXie C, Chau H-F, Zhang J-X, et al., 2019,
Bladder Cancer Photodynamic Therapeutic Agent with Off-On Magnetic Resonance Imaging Enhancement
, ADVANCED THERAPEUTICS, Vol: 2- Author Web Link
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- Citations: 18
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Journal articleMundil R, Wilson LE, Schaarschmidt D, et al., 2019,
Redox-switchable α-diimine palladium catalysts for control of polyethylene topology
, Polymer, Vol: 179, ISSN: 0032-3861A series of palladium complexes bearing ferrocene substituted α-diimine ligands was synthesized and investigated for ethene polymerization at different conditions to modulate the extent of “chain-walking” mechanism and regulate branching and topology of resulting polyethylenes. All ferrocene substituted complexes catalyzed living/controlled ethene polymerization. The ability of ferrocene substituted palladium complexes to provide polyethylenes with dendritic topology was proved by measuring their Mark-Houwink plots. In-situ chemical oxidation of ferrocene moieties via silver triflate was used to affect the catalyst electronic structure and support the “chain-walking” mechanism. Oxidation of palladium catalyst led to its destabilization while the catalytic activity of newly formed sites was substantially increased. It was demonstrated that catalyst oxidation is a powerful tool to regulate the topology of resulting polyethylenes.
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Conference paperBoyle J, Seneviratne A, Han Y, et al., 2019,
VERTEBRATE HEMATOMA RESOLUTION IS DIRECTED BY ACTIVATING TRANSCRIPTION FACTOR 1 (ATF1) AND ADENOSINE-MONOPHOSPHATE-ACTIVATED-PROTEIN-KINASE (AMPK)
, 87th Congress of the European-Atherosclerosis-Society (EAS), Publisher: ELSEVIER IRELAND LTD, Pages: E246-E246, ISSN: 0021-9150 -
Journal articleWang L, Long NJ, Li L, et al., 2019,
Multi-functional bismuth-doped bioglasses: combining bioactivity and photothermal response for bone tumor treatment and tissue repair (vol 7, 1, 2018)
, LIGHT-SCIENCE & APPLICATIONS, Vol: 8, ISSN: 2047-7538 -
Journal articleMiller P, Apps S, Long N, 2019,
Cobalt(-I) triphos dinitrogen complexes: activation and silyl-functionalisation of N2
, Chemical Communications, Vol: 55, Pages: 6579-6582, ISSN: 1359-7345The cobalt dinitrogen complexes [{(EP3Ph)Co(μ-N2)}2Mg(THF)4], with triphos ligand scaffolds (EP3Ph, E = N or CMe), were prepared via two electron reductions of the Co(I) precursors [CoCl(EP3Ph)]. Both complexes showed high degrees of N2 activation owing to the formation of a rare M–NN–Mg–NN–M bridging-magnesium core. These systems showed further N2 functionalisation reactivity by silylation, forming silyldiazenido complexes [(EP3Ph)Co(NNSiMe3)].
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Journal articleMann PB, Afzal K, Long NJ, et al., 2019,
A glassware- free combinatorial synthesis of green quantum dots using bubble wrap
, RSC ADVANCES, Vol: 9, Pages: 16851-16855, ISSN: 2046-2069 -
Journal articleMorse SV, Pouliopoulos AN, Chan TG, et al., 2019,
Rapid short-pulse ultrasound delivers drugs uniformly across the murine blood-brain barrier with negligible disruption
, Radiology, Vol: 291, Pages: 459-466, ISSN: 0033-8419Background Previous work has demonstrated that drugs can be delivered across the blood-brain barrier by exposing circulating microbubbles to a sequence of long ultrasound pulses. Although this sequence has successfully delivered drugs to the brain, concerns remain regarding potentially harmful effects from disrupting the brain vasculature. Purpose To determine whether a low-energy, rapid, short-pulse ultrasound sequence can efficiently and safely deliver drugs to the murine brain. Materials and Methods Twenty-eight female wild-type mice underwent focused ultrasound treatment after injections of microbubbles and a labeled model drug, while three control mice were not treated (May-November 2017). The left hippocampus of 14 mice was exposed to low-energy short pulses (1 MHz; five cycles; peak negative pressure, 0.35 MPa) of ultrasound emitted at a rapid rate (1.25 kHz) in bursts (0.5 Hz), and another 14 mice were exposed to standard long pulses (10 msec, 0.5 Hz) containing 150 times more acoustic energy. Mice were humanely killed at 0 (n = 5), 10 (n = 3), or 20 minutes (n = 3) after ultrasound treatment. Hematoxylin-eosin (H-E) staining was performed on three mice. The delivered drug dose and distribution were quantified with the normalized optical density and coefficient of variation. Safety was assessed by H-E staining, the amount of albumin released, and the duration of permeability change in the blood-brain barrier. Statistical analysis was performed by using the Student t test. Results The rapid short-pulse sequence delivered drugs uniformly throughout the parenchyma. The acoustic energy emitted from the microbubbles also predicted the delivered dose (r = 0.97). Disruption in the blood-brain barrier lasted less than 10 minutes and 3.4-fold less albumin was released into the brain than with long pulses. No vascular or tissue damage from rapid short-pulse exposure was observable using H-E staining. Conclusion The rapid short-pulse ultrasound sequence is a minimally
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Journal articleHernandez-Gil J, Braga M, Harriss B, et al., 2019,
Development of Ga-68-labelled ultrasound microbubbles for whole-body PET imaging
, Chemical Science, Vol: 10, Pages: 5603-5615, ISSN: 2041-6520Microbubble (MB) contrast agents have revolutionalised the way ultrasound (US) imaging can be used clinically and pre-clinically. Contrast-enhanced US offers improvements in soft-tissue contrast, as well as the ability to visualise disease processes at the molecular level. However, its inability to provide in vivo whole-body imaging can hamper the development of new MB formulations. Herein, we describe a fast and efficient method for achieving 68Ga-labelling of MBs after a direct comparison of two different strategies. The optimised approach produces 68Ga-labelled MBs in good yields through the bioorthogonal inverse-electron-demand Diel–Alder reaction between a trans-cyclooctene-modified phospholipid and a new tetrazine-bearing HBED-CC chelator. The ability to noninvasively study the whole-body distribution of 68Ga-labelled MBs was demonstrated in vivo using positron emission tomography (PET). This method could be broadly applicable to other phospholipid-based formulations, providing accessible solutions for in vivo tracking of MBs.
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Journal articleLeow CH, Bush N, Stanziola A, et al., 2019,
3D microvascular imaging using high frame rate ultrasound and ASAP without contrast agents: development and initial in vivo evaluation on non-tumour and tumour models
, IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control, Vol: 66, Pages: 939-948, ISSN: 0885-3010Three-dimensional imaging is valuable to non-invasively assess angiogenesis given the complex 3D architecture of vascular networks. The emergence of high frame rate (HFR) ultrasound, which can produce thousands of images per second, has inspired novel signal processing techniques and their applications in structural and functionalimaging of blood vessels. Although highly sensitive vascular mapping has been demonstrated using ultrafast Doppler, the detectability of microvasculature from the background noise may be hindered by the low signal to noise ratio (SNR) particularly in deeper region and without the use of contrast agents. We have recently demonstrated a coherence based technique, acoustic sub-aperture imaging (ASAP), for super-contrast vascular imaging and illustrated the contrast improvement using HFR contrast-enhanced ultrasound. In this work, we provide a feasibility study for microvascular imaging using ASAP without contrast agents, and extend its capability from 2D to volumetric vascular mapping. Using an ultrasound research system and a pre-clinical probe, we demonstrated the improved visibility of microvascular mapping using ASAP in comparison to ultrafast Power Doppler (PD) on a mouse kidney, liver and tumour without contrast agent injection. The SNR of ASAP images improves in average by 10dB when compared to PD. Besides, directional velocity mappings were also demonstrated by combining ASAP with the phase information extracted from lag-1 autocorrelation. Three-dimensional vascular and velocity mapping of the mouse kidney, liver and tumour were demonstrated by stackingthe ASAP images acquired using 2D ultrasound imaging and a trigger-controlled linear translation stage. The 3D results depicted clear micro-vasculature morphologies and function
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Journal articleZhang G, Lin S, Leow CH, et al., 2019,
Quantification of vaporized targeted nanodroplets using high-frame-rate ultrasound and optics
, Ultrasound in Medicine and Biology, Vol: 45, Pages: 1131-1142, ISSN: 0301-5629Owing to their ability to efficiently deliver biological cargo and sense the intracellular milieu, vertical arrays of high aspect ratio nanostructures, known as nanoneedles,are being developed as minimally invasive tools for cell manipulation. However, little is known of the mechanisms of cargo transfer across the cell membrane-nanoneedle interface. Particularly,the contributions of membrane piercing, modulation of membrane permeability and endocytosis to cargo transfer remain largelyunexplored. Here, combining state-of-the-art electron and scanning ion conductance microscopy with molecular biology techniques, we show that porous silicon nanoneedle arrays concurrently stimulate independent endocytic pathways which contribute to enhanced biomolecule delivery into human mesenchymal stem cells. Electron microscopy of the cell membrane at nanoneedle sites shows an intact lipid bilayer, accompanied by an accumulation of clathrin-coated pits and caveolae. Nanoneedles enhance the internalisation of biomolecular markers of endocytosis, highlighting the concurrent activation of caveolae-and clathrin-mediated endocytosis, alongside macropinocytosis. These events contribute to the nanoneedle-mediated delivery (nanoinjection) of nucleic acids into human stem cells, which distribute across the cytosol and the endolysosomal system. This data extends the understanding of how nanoneedles modulate biological processes to mediate interaction with the intracellular space, providing indications for the rational design of improved cell-manipulation technologies.
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Conference paperCooper S, Yue T, Miller P, et al., 2019,
Tripodal N-centred phosphine ligands: Towards a novel donor set for <SUP>99m</SUP>Tc and <SUP>186/188</SUP>Re radiopharmaceutical formulation
, Publisher: WILEY, Pages: S295-S296, ISSN: 0362-4803 -
Journal articlePensa E, Karpowicz R, Jabaoński A, et al., 2019,
Gold-Induced Desulfurization in a Bis(ferrocenyl) Alkane Dithiol
, Organometallics, ISSN: 0276-7333© 2019 American Chemical Society. Thiol-modified ferrocenes on gold have been archetypical model systems for many fundamental charge transfer and other studies, since both thiol-gold and ferrocene redox chemistry are considered to be well-understood. Thus unexpectedly, we found that for a representative of a new class of flexibly linked bis-ferrocenyl compounds, namely, 1-10-bis(1-ferrocenyl)decane dithiol, surface immobilization on gold failed. Instead, in the presence of gold, molecular decomposition took place, resulting in sulfur-based adlayers and well-defined molecular elimination products, for which we provide spectroscopic evidence. Careful control experiments and comparison with related ferrocene compounds provide insight into the mechanism of the observed elimination reactions, as a combined effect of the molecular structure and the nature of the gold/sulfur bond. These findings, thus, have a broader impact on the design of molecular adlayers, for example, in the context of surface functionalization in sensing or the synthesis of gold nanoparticles.
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Conference paperLeber R, Wilson L, Robaschik P, et al., 2019,
Vacuum deposition of biferrocene thin films: growth strategies for stability and tuneable magnetism
, 257th National Meeting of the American-Chemical-Society (ACS), Publisher: AMER CHEMICAL SOC, ISSN: 0065-7727
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Contact
Professor Nick Long
Email: n.long@imperial.ac.uk
Telephone: +44 (0)20 7594 5781
Location
501J
Molecular Sciences Research Hub
White City Campus
