Scientific Publications

Peer Reviewed Articles, Conference Posters, Publications on Technology

The Effects of Polymer Topology and Chain Length on the Antimicrobial Activity and Hemocompatibility of Amphiphilic Ternary Copolymers

Polymer Chemistry Journal

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Abstract

Investigation into the macromolecular structure-activity relationship of synthetic antimicrobial polymers has been gaining scientific interests due to possibility of discovering new alternatives for combating the rise of multidrug resistance in bacteria. Recently, we reported the development of new antimicrobial polymers in the form of amphiphilic ternary copolymers that consist of low-fouling (oligoethylene glycol), cationic and hydrophobic side chains. The combination of these three main functional groups is crucial in endowing the polymers with high antimicrobial potency against Gram-negative pathogens and low cytotoxicity. Following on from our previous study, we herein present a systematic assessment on the effects of polymer chain length and architecture (i.e., random vs block copolymers, and linear vs hyperbranched) on the antimicrobial activity and hemocompatibility of antimicrobial ternary copolymers. The polymer chain length in random copolymers slightly affects the antimicrobial activity where longer chains are marginally more bacteriostatic against Pseudomonas aeruginosa and Escherichia coli. In terms of hemocompatibility, polymers with shorter chains are more prone to hemaagglutination. Interestingly, when the hydrophilic and hydrophobic segments are separated into diblock copolymers, the antimicrobial activity is lost, possibly due to the stable core-shell architecture. The hyperbranched structure which consists of 2-ethylhexyl groups as hydrophobic side-chains yields the best overall biological properties, having similar antimicrobial activity (MIC = 64 μg mL–1) and > 4-fold increase in HC50 compared to the linear random copolymers (HC50 > 10000 μg mL–1) with no hemaagglutination. The hyperbranched polymers are also bactericidal and kill ≥ 99% and 90% of planktonic and biofilm Pseudomonas aeruginosa, respectively. This study thus highlights the importance of determining macromolecular structural aspects that govern the biological activity of antimicrobial polymers.

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Facile preparation of full-color emissive carbon dots and their applications in imaging of the adhesion of erythrocytes to endothelial cells

Journal of Materials Chemistry B

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Abstract

Full-color emissive CDs (F-CDs) are synthesized by a green method, which avoids toxic reagents, harsh reaction conditions and multistep processes. The water-soluble, 6 ± 1 nm uniform-sized F-CDs exhibit tunable multicolor emission in gradient colors from blue to red. The emission wavelength and intensity of the fluorescence and the wavelength of the absorption peak can be tuned by controlling the concentration of the F-CD aqueous dispersions. The remarkable low cytotoxicity, good photostability and successful application in imaging of the adhesion of erythrocytes to endothelial cells demonstrate the great applicability of the F-CDs as multiplexed bioimaging reagents. The present research not only offers a facile, green, one-pot method for the preparation of F-CDs, but also presents a novel, experimentally convenient research mode for studying cellular functions and provides useful enlightenment for enlarging the application fields of CDs.

Graphical abstract: Facile preparation of full-color emissive carbon dots and their applications in imaging of the adhesion of erythrocytes to endothelial cells

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The selexipag active metabolite ACT-333679 displays strong anti-contractile and anti- remodeling effects, but low β-arrestin recruitment and desensitization potential

The Journal of Pharmacology and Experimental Therapeutics, 2017

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John Gatfield, Katalin Menyhart, Daniel Wanner, Carmela Gnerre, Lucile Monnier, Keith Morrison, Patrick Hess, Marc Iglarz, Martine Clozel and Oliver Nayler.

Abstract

Prostacyclin (PGI2) receptor (IP receptor) agonists, which are indicated for the treatment of pulmonary arterial hypertension (PAH), increase cytosolic cAMP levels and thereby inhibit pulmonary vasoconstriction, pulmonary arterial smooth muscle cell (PASMC) proliferation and extracellular matrix synthesis. Selexipag (Uptravi®) is the first non-prostanoid IP receptor agonist, it is available orally and was recently approved for the treatment of PAH. In this study we show that the active metabolite of selexipag and the main contributor to clinical efficacy, ACT-333679 (previously known as MRE-269), behaved as full agonist in multiple PAH-relevant receptor-distal – or downstream – cellular readouts with a maximal efficacy comparable to that of the prototypic PGI2analog iloprost: In PASMC, ACT-333679 potently induced cellular relaxation (EC50=4.3 nM), inhibited cell proliferation (IC50=4.0 nM) as well as extracellular matrix synthesis (IC50=8.3 nM). In contrast, ACT-333679 displayed partial agonism in receptor-proximal – or upstream – cAMP accumulation assays (Emax=56%) when compared to iloprost (Emax=100%) and the PGI2 analogs beraprost and treprostinil. Partial agonism of ACT-333679 also resulted in limited β-arrestin recruitment (Emax=40%) and lack of sustained IP receptor internalization, whereas all tested PGI2analogs behaved as full agonists in these desensitization-related assays. In line with these in vitro findings, selexipag, but not treprostinil, displayed sustained efficacy in rat models of pulmonary and systemic hypertension. Thus, the partial agonism of ACT-333679 allows for full efficacy in amplified receptor-distal PAH-relevant readouts while causing limited activity in desensitization-related receptor-proximal readouts.

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Live Single-cell Mass Spectrometry with Spatial Quantitation by Three-Dimensional Holographic and Tomographic Laser Microscopy

Analytical Sciences as Rapid Communication, 2016

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Ali A, Abouleila Y, Amer S, Furushima R, Emara S, Equis S, Cotte Y, Masujima T

Abstract

The locations and volumes of the contents of a single HepG2 cell were visualized under three-dimensional (3D) holographic and tomographic (HT) laser microscopy, colored by refractive index, not staining. After trapping the specific area of a target cell in a nanospray tip, quantification was performed by live single-cell mass spectrometry. Comparison of the HepG2 cells’ before and after 3D-HT images allowed the inference of the precise volume and original location of the trapped cell contents. The total amount of a trapped molecule was estimated. The images also revealed morphological changes in the cell structure caused by the manipulation.

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Tomographic Holographic Microscopy for Nano-Scale Dose Calculation and Assessing Gold Nanoparticle Uptake in Live Cells

ASTRO 2016

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Grassberger C, Dinkelborg P, McNamara A, Schuemann J, McMahon S*, Willers H, Paganetti H, Wang M

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Nanomicroscopy for Live Cell tomography

The Handbook of Nanomedicine, Third Edition, 2017

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„Nanolive‘s Cell Explorer‘s technology enables determination of how light propagets through the cell [… ] Applications of this technology, which is commercially available, will enable discoveries on living cells and study of diseases as well as effects of drugs at cell level. It will be useful for recording celular uptake as well as localization of metal nanoparticles and assessments of cell exposure to nanoparticles.“

Characterising live cell behaviour: Traditional label-free and quantitative phase imaging approaches

The International Journal of Biochemistry & Cell Biology, 2017

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“2.2. Quantitative phase imaging:  Commercially-available QPI systems can be broadly classified according to the phase retrieval method utilised: (i) off-axis digital holography (PhiAB, Nanolive, Lyncee Tec, Tescan,1 Ovizio); (ii) wavefront sensing (Phasics); (iii) spatial light interference (Phi Optics); (iv) ptychography (Phasefocus).”