15 research outputs found
Dynamics of ion-regulated photoinduced electron transfer in BODIPY-BAPTA conjugates
International audienceEfficient Ca2+-switched fluorescent sensors, where fluorescence output is governed by a light-activated ion-gated electron transfer pathway, can be obtained on combining BODIPY chromophores with a readily oxidized biocompatible and selective BAPTA receptor. Herein we report the synthesis and studies of two such conjugates, which vary in the nature of the spacer separating the two electroactive components, namely none (1) or phenyl (2). Single crystal X-ray crystallography and molecular modelling structures and calculations give information on molecular and electronic structure, while steady-state fluorescence experiments show high Ca2+-induced fluorescence enhancement factors of 122 and 23 and Kd values of 0.50 ÎŒM and 0.13 ÎŒM for 1 and 2, respectively. Notably, studies of the ultrafast photoinduced processes (through transient absorption spectroscopy) give access to electron transfer dynamics in pseudophysiological media as well as in a polar non-protic solvent and information about the fate of the excited molecules in the presence and absence of calcium. In water, electron transfer rates as high as 3.3 Ă 1012 sâ1 and 8.3 Ă 1011 sâ1 are measured for the ion-free, directly connected conjugate and the variant incorporating a phenyl spacer, respectively. This electron transfer pathway is efficiently blocked by the presence of an ion, restoring fluorescence
Tunable Semiconducting Polymer Nanoparticles with INDT-Based Conjugated Polymers for Photoacoustic Molecular Imaging.
Photoacoustic imaging combines both excellent spatial resolution with high contrast and specificity, without the need for patients to be exposed to ionizing radiation. This makes it ideal for the study of physiological changes occurring during tumorigenesis and cardiovascular disease. In order to fully exploit the potential of this technique, new exogenous contrast agents with strong absorbance in the near-infrared range, good stability and biocompatibility, are required. In this paper, we report the formulation and characterization of a novel series of endogenous contrast agents for photoacoustic imaging in vivo. These contrast agents are based on a recently reported series of indigoid Ï-conjugated organic semiconductors, coformulated with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, to give semiconducting polymer nanoparticles of about 150 nm diameter. These nanoparticles exhibited excellent absorption in the near-infrared region, with good photoacoustic signal generation efficiencies, high photostability, and extinction coefficients of up to three times higher than those previously reported. The absorption maximum is conveniently located in the spectral region of low absorption of chromophores within human tissue. Using the most promising semiconducting polymer nanoparticle, we have demonstrated wavelength-dependent differential contrast between vasculature and the nanoparticles, which can be used to unambiguously discriminate the presence of the contrast agent in vivo
Development of lipopolyplexes for gene delivery: a comparison of the effects of differing modes of targeting peptide display on the structure and transfection activities of lipopolyplexes
The design, synthesis and formulation of nonâviral gene delivery vectors is an area of renewed research interest. Amongst the most efficient nonâviral gene delivery systems are lipopolyplexes, in which cationic peptides are coâformulated with plasmid DNA and lipids. One advantage of lipopolyplex vectors is that they have the potential to be targeted to specific cell types by attaching peptide targeting ligands on the surface, thus increasing both the transfection efficiency and selectivity for disease targets such as cancer cells. In this paper, we have investigated two different modes of displaying cellâspecific peptide targeting ligands at the surface of lipopolyplexes. Lipopolyplexes formulated with bimodal peptides, with both receptor binding and DNA condensing sequences, were compared with lipopolyplexes with the peptide targeting ligand directly conjugated to one of the lipids. Three EGFR targeting peptide sequences were studied, together with a range of lipid formulations and maleimide lipid structures. The biophysical properties of the lipopolyplexes and their transfection efficiencies in a basalâlike breast cancer cell line were investigated using plasmid DNA bearing genes for the expression of firefly luciferase and green fluorescent protein. Fluorescence quenching experiments were also used to probe the macromolecular organisation of the peptide and pDNA components of the lipopolyplexes. We demonstrated that both approaches to lipopolyplex targeting give reasonable transfection efficiencies, and the transfection efficiency of each lipopolyplex formulation is highly dependent on the sequence of the targeting peptide. To achieve maximum therapeutic efficiency, different peptide targeting sequences and lipopolyplex architectures should be investigated for each target cell type
Communication moléculaire biomimétique entre molécules et nanosystÚmes photocontrÎlés en compartiments confinés
The thesis focuses on the study and design of novel photoactive molecules and their application as labeling agents, fluorescent molecular Ca2+-sensors and photolabile Ca2+-decaging agents in aqueous media and organized supramolecular assemblies. The designed fluorophores are based on boron-dipyrromethene (BODIPY) bearing hydrophobic chains or a reactive group like an azide or a perfluorophenyl moiety. Biocompatible calcium receptors have been prepared harnessing the fluorescence properties of BODIPY, naphthalimide and furan fluorophores. The development of self-assembled multicompartmentalized architectures, namely fluorocarbon vesicles in giant polymersomes is reported and the system has been used to create white light emission in confined microdomains. The Ca2+-based ion transfer ion the confined polymer compartments between individual fluorinated vesicles has been studied. The ion transfer in between vesicles in polymer microcompartments has been established as an artificial prototype system for cellular communication.Cette thĂšse se focalise sur la synthĂšse et l'Ă©tude de nouvelles molĂ©cules photoactives et leurs applications en tant que marqueurs, senseurs molĂ©culaires et rĂ©cepteurs dâions photomodulables en milieux aqueux et organisĂ©s. Les fluorophores dĂ©veloppĂ©s sont principalement des dĂ©rivĂ©s du bore-dipyromĂ©thene (BODIPY), comportant des groupements rĂ©actifs (azoture, perfluorophĂ©nyle), des chaines hydrophobes, ou sont intĂ©grĂ©s Ă un rĂ©cepteur de calcium biocompatible. Le dĂ©veloppement d'architectures auto-assemblĂ©es multicompartimentĂ©es de type vĂ©sicules dans des polymersomes gĂ©ant y est dĂ©crit. Ces architectures ont Ă©tĂ© utilisĂ©es pour la gĂ©nĂ©ration de lumiĂšre blanche dans un micro-domaine, et constitue un modĂšle pour l'Ă©tude de transfert d'ions calcium entre vĂ©sicules localisĂ©es dans des polymersomes individuels. Ce transfert entre nano-objets confinĂ©s Ă l'intĂ©rieur d'un polymersome gĂ©ant reprĂ©sente un systĂšme prototype de communication cellulaire artificiel rudimentaire
Photocontrolled biomimetic communication between molecules and nanosystems in confined compartments
Cette thĂšse se focalise sur la synthĂšse et l'Ă©tude de nouvelles molĂ©cules photoactives et leurs applications en tant que marqueurs, senseurs molĂ©culaires et rĂ©cepteurs dâions photomodulables en milieux aqueux et organisĂ©s. Les fluorophores dĂ©veloppĂ©s sont principalement des dĂ©rivĂ©s du bore-dipyromĂ©thene (BODIPY), comportant des groupements rĂ©actifs (azoture, perfluorophĂ©nyle), des chaines hydrophobes, ou sont intĂ©grĂ©s Ă un rĂ©cepteur de calcium biocompatible. Le dĂ©veloppement d'architectures auto-assemblĂ©es multicompartimentĂ©es de type vĂ©sicules dans des polymersomes gĂ©ant y est dĂ©crit. Ces architectures ont Ă©tĂ© utilisĂ©es pour la gĂ©nĂ©ration de lumiĂšre blanche dans un micro-domaine, et constitue un modĂšle pour l'Ă©tude de transfert d'ions calcium entre vĂ©sicules localisĂ©es dans des polymersomes individuels. Ce transfert entre nano-objets confinĂ©s Ă l'intĂ©rieur d'un polymersome gĂ©ant reprĂ©sente un systĂšme prototype de communication cellulaire artificiel rudimentaire.The thesis focuses on the study and design of novel photoactive molecules and their application as labeling agents, fluorescent molecular Ca2+-sensors and photolabile Ca2+-decaging agents in aqueous media and organized supramolecular assemblies. The designed fluorophores are based on boron-dipyrromethene (BODIPY) bearing hydrophobic chains or a reactive group like an azide or a perfluorophenyl moiety. Biocompatible calcium receptors have been prepared harnessing the fluorescence properties of BODIPY, naphthalimide and furan fluorophores. The development of self-assembled multicompartmentalized architectures, namely fluorocarbon vesicles in giant polymersomes is reported and the system has been used to create white light emission in confined microdomains. The Ca2+-based ion transfer ion the confined polymer compartments between individual fluorinated vesicles has been studied. The ion transfer in between vesicles in polymer microcompartments has been established as an artificial prototype system for cellular communication
A prototype reversible polymersome-stabilized H2S photoejector operating under pseudophysiological conditions
Persistent self-assembled polymersome capsules are shown to solubilise and stabilize a new hydrosulfide-containing (2), as well as hydroxylated (1), malachite green derivatives in their leuco-forms in aqueous buffer solution. Photoirradiation resulted in reversible hydroxide release/hydrogen sulfide generation. Notably, the efficient augmentation of H2S concentration to physiologically-relevant levels is shown
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Tunable Semiconducting Polymer Nanoparticles with INDT-Based Conjugated Polymers for Photoacoustic Molecular Imaging.
Photoacoustic imaging combines both excellent spatial resolution with high contrast and specificity, without the need for patients to be exposed to ionizing radiation. This makes it ideal for the study of physiological changes occurring during tumorigenesis and cardiovascular disease. In order to fully exploit the potential of this technique, new exogenous contrast agents with strong absorbance in the near-infrared range, good stability and biocompatibility, are required. In this paper, we report the formulation and characterization of a novel series of endogenous contrast agents for photoacoustic imaging in vivo. These contrast agents are based on a recently reported series of indigoid Ï-conjugated organic semiconductors, coformulated with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, to give semiconducting polymer nanoparticles of about 150 nm diameter. These nanoparticles exhibited excellent absorption in the near-infrared region, with good photoacoustic signal generation efficiencies, high photostability, and extinction coefficients of up to three times higher than those previously reported. The absorption maximum is conveniently located in the spectral region of low absorption of chromophores within human tissue. Using the most promising semiconducting polymer nanoparticle, we have demonstrated wavelength-dependent differential contrast between vasculature and the nanoparticles, which can be used to unambiguously discriminate the presence of the contrast agent in vivo
Dynamics of ion-regulated photoinduced electron transfer in BODIPY-BAPTA conjugates
Efficient Ca2+-switched fluorescent sensors, where fluorescence output is governed by a light-activated ion-gated electron transfer pathway, can be obtained on combining BODIPY chromophores with a readily oxidized biocompatible and selective BAPTA receptor. Herein we report the synthesis and studies of two such conjugates, which vary in the nature of the spacer separating the two electroactive components, namely none (1) or phenyl (2). Single crystal X-ray crystallography and molecular modelling structures and calculations give information on molecular and electronic structure, while steady-state fluorescence experiments show high Ca2+-induced fluorescence enhancement factors of 122 and 23 and Kd values of 0.50 ÎŒM and 0.13 ÎŒM for 1 and 2, respectively. Notably, studies of the ultrafast photoinduced processes (through transient absorption spectroscopy) give access to electron transfer dynamics in pseudophysiological media as well as in a polar non-protic solvent and information about the fate of the excited molecules in the presence and absence of calcium. In water, electron transfer rates as high as 3.3 Ă 1012 sâ1 and 8.3 Ă 1011 sâ1 are measured for the ion-free, directly connected conjugate and the variant incorporating a phenyl spacer, respectively. This electron transfer pathway is efficiently blocked by the presence of an ion, restoring fluorescence.Communication between Functional Molecules using Photocontrolled Ion
Facile functionalization of a fully fluorescent perfluorophenyl BODIPY: photostable thiol and amine conjugates
Selective nucleophilic substitution on a perfluorophenyl unit comprising a BODIPY fluorophore using an alkanethiol or a primary amine offers a quantitative fluorophore labelling strategy, while retaining high photostability and emission quantum yields approaching unity.Communication between Functional Molecules using Photocontrolled Ion
International evaluation of injury rates in coal mining: A comparison of risk and compliance-based regulatory approaches
It is unknown if either of the two dominant regulatory approaches commonly employed in the mining industry to oversee occupational health and safety is superior in terms of reducing workplace injuries. In effort to answer this question, the following study analyzed annual lost-time injury (LTI) rates for bituminous coal mines in the United States (US) with respect to Queensland (QLD) and New South Wales (NSW), Australia from 1996 to 2003. Using the available data sources, changes in the occurrences of accidents and injuries were contrasted between each of these regions. The relationship between secular trends in injury rates and changes in the Australian regulatory structure from compliance-based to a risk-based approach was examined to see if evidence existed that the implementation of risk-based regulatory systems may be associated with substantive improvement in employee safety. Generalized estimating equations were constructed to analyze rates of change in incident rate ratios (IRR) of LTIs among coal mines. From 1996 to 2003, LTIs per 100,000 miners declined 20% in the US as compared with 78% and 52% in QLD and NSW, and the adjusted IRR for each region decreased by 11%, 72% and 44%, respectively. The application of risk-based health and safety regulations in Australia provides one explanation for the differential decline in LTIs among Australian states when compared to the US