Magazine Articles |
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Nodin, L., Méallet-Renault, R., & Piard, J. (2014). Séparation et étude des pigments des épinards par spectrofluorimétrie. Bulletin de l’Union des Physiciens, 961, 293–310.
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Peer-reviewed Publications |
Bon, P., Lécart, S., Fort, E., & Lévêque-Fort, S. (2014). Fast Label-Free Cytoskeletal Network Imaging in Living Mammalian Cells. Biophysical Journal, 106(8), 1588–1595.
Résumé: We present a full-field technique that allows label-free cytoskeletal network imaging inside living cells. This noninvasive technique allows monitoring of the cytoskeleton dynamics as well as interactions between the latter and organelles on any timescale. It is based on high-resolution quantitative phase imaging (modified Quadriwave lateral shearing interferometry) and can be directly implemented using any optical microscope without modification. We demonstrate the capability of our setup on fixed and living Chinese hamster ovary cells, showing the cytoskeleton dynamics in lamellipodia during protrusion and mitochondria displacement along the cytoskeletal network. In addition, using the quantitative function of the technique, along with simulation tools, we determined the refractive index of a single tubulin microtubule to be ntubu=2.36±0.6 at ?=527 nm.
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Celia, E., Amigoni, S., de Givenchy, E. T., Pieters, G., Gaucher, A., Prim, D., Audibert, J. F., Meallet-Renault, R., Pansu, R., & Guittard, F. (2014). A spiral designed surface based on amino-perylene grafted polyacrylic acid. Chemical Communications, 50(81), 12034–12036.
Résumé: This communication shows the possibility of inducing spontaneous special surface organisation by means of grafting a fluorescent aminobenzo[g,h,i]perylene derivative onto surface grown polyacrylic chains.
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Deshayes, S., & Gref, R. (2014). Synthetic and bioinspired cage nanoparticles for drug delivery. Nanomedicine, 9(10), 1545–1564.
Résumé: Nanotechnology has the potential to revolutionize drug delivery, but still faces some limitations. One of the main issues regarding conventional nanoparticles is their poor drug-loading and their early burst release. Thus, to overcome these problems, researchers have taken advantage of the host-guest interactions that drive some assemblies to form cage molecules able to strongly entrap their cargo and design new nanocarriers called cage nanoparticles. These systems can be classified into two categories: bioinspired nanosystems such as virus-like particles, ferritin, small heat shock protein: and synthetic host-guest supramolecular systems that require engineering to actually form supramolecular nanoassemblies. This review will highlight the recent advances in cage nanoparticles for drug delivery with a particular focus on their biomedical applications.
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Grazon, C., Rieger, J., Charleux, B., Clavier, G., & Meallet-Renault, R. (2014). Ultrabright BODIPY-Tagged Polystyrene Nanoparticles: Study of Concentration Effect on Photophysical Properties. Journal Of Physical Chemistry C, 118(25), 13945–13952.
Résumé: Fluorescent nanomaterials are invaluable tools for bioimaging. Polymeric nanoparticles labeled with organic dyes are very promising for this purpose. It is thus very important to fully understand their photophysical properties. New fluorescent core-shell nanoparticles have been prepared. The outer part is a poly(ethylene glycol)-block-poly(acrylic acid) copolymer, and the core is a copolymer of styrene and methacrylic BODIPY fluorophore. The hydrophilic and hydrophobic parts are covalently linked, ensuring both stability and biocompatibility. We prepared nanoparticles with increasing amounts of BODIPY, from 500 to 5000 fluorophores per particles. Increasing the concentration of BODIPY lowers both the fluorescence quantum yield and the lifetime. However, the brightness of the individual particles increases up to 8 X 10(7). To understand the loss of fluorescence efficiency, fluorescence decays have been recorded and fitted with a mathematical model using a stretched exponential function. This result gives an insight into the fluorophore arrangement within the hydrophobic core.
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Meance, S., Gamby, J., Faure, M., Kou, Q. L., & Haghiri-Gosnet, A. M. (2014). Electrochemiluminescence on-a-chip: Towards a hand-held electrically powered optofluidic source. Talanta, 129, 150–154.
Résumé: We report a microfluidic platform that integrates several parallel optical sources based on electrochemiluminescence (ECL) of 9,10-diphenylanthracene (DPA) as luminophore agent. The annihilation of DPA radicals provides a low wavelength emission at lambda=430 nm in the blue-visible range. By varying the distance between electrodes for each ECL integrated source, this glass/PDMS/glass platform enabled a systematic investigation of the main electrochemical parameters involved in ECL These parameters have been studied either in a static mode or in a dynamic one. Even at slow flow rate (similar to 2 μl s(-1)), the renewal of electroactive species could be easily promoted inside the microfluidic channel which gives rise to a stable optical intensity for several minutes. Compared with traditional optically pumped dye sources, this microfluidic system demonstrates that ECL can be easily implemented on chip for producing much compact optofluidic sources. Such simply electrically powered system-on-chip would surely encourage the future of hand-held μTAS devices with integrated fast detection and embedded electronics. (C) 2014 Elsevier B.V. All rights reserved.
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Monsel, A., Lecart, S., Roquilly, A., Broquet, A., Jacqueline, C., Mirault, T., Troude, T., Fontaine-Aupart, M. - P., & Asehnoune, K. (2014). Analysis of Autofluorescence in Polymorphonuclear Neutrophils: A New Tool for Early Infection Diagnosis. PLOS ONE, 9(3), 1790–1800.
Résumé: Diagnosing bacterial infection (BI) remains a challenge for the attending physician. An ex vivo infection model based on human fixed polymorphonuclear neutrophils (PMNs) gives an autofluorescence signal that differs significantly between stimulated and unstimulated cells. We took advantage of this property for use in an in vivo pneumonia mouse model and in patients hospitalized with bacterial pneumonia. A 2-fold decrease was observed in autofluorescence intensity for cytospined PMNs from broncho-alveolar lavage (BAL) in the pneumonia mouse model and a 2.7-fold decrease was observed in patients with pneumonia when compared with control mice or patients without pneumonia, respectively. This optical method provided an autofluorescence mean intensity cut-off, allowing for easy diagnosis of BI. Originally set up on a confocal microscope, the assay was also effective using a standard epifluorescence microscope. Assessing the autofluorescence of PMNs provides a fast, simple, cheap and reliable method optimizing the efficiency and the time needed for early diagnosis of severe infections. Rationalized therapeutic decisions supported by the results from this method can improve the outcome of patients suspected of having an infection.
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Porcel, E., Tillement, O., Lux, F., Mowat, P., Usami, N., Kobayashi, K., Furusawa, Y., Le Sech, C., Li, S., & Lacombe, S. (2014). Gadolinium-based nanoparticles to improve the hadrontherapy performances. NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE, 10(8), 1601–1608.
Résumé: Nanomedicine is proposed as a novel strategy to improve the performance of radiotherapy. High-Z nanoparticles are known to enhance the effects of ionizing radiation. Recently, multimodal nanoparticles such as gadolinium-based nanoagents were proposed to amplify the effects of x-rays and g-rays and to improve MRI diagnosis. For tumors sited in sensitive tissues, childhood cases and radioresistant cancers, hadrontherapy is considered superior to x-rays and g-rays. Hadrontherapy, based on fast ion radiation, has the advantage of avoiding damage to the tissues behind the tumor; however, the damage caused in front of the tumor is its major limitation. Here, we demonstrate that multimodal gadolinium-based nanoparticles amplify cell death with fast ions used as radiation. Molecular scale experiments give insights into the mechanisms underlying the amplification of radiation effects. This proof-of-concept opens up novel perspectives for multimodal nanomedicine in hadrontherapy, ultimately reducing negative radiation effects in healthy tissues in front of the tumor. From the Clinical Editor: Gadolinium-chelating polysiloxane nanoparticles were previously reported to amplify the anti-tumor effects of x-rays and g-rays and to serve as MRI contrast agents. Fast ion radiation-based hadrontherapy avoids damage to the tissues behind the tumor, with a major limitation of tissue damage in front of the tumor. This study demonstrates a potential role for the above nanoagents in optimizing hadrontherapy with preventive effects in healthy tissue and amplified cell death in the tumor. (C) 2014 Elsevier Inc. All rights reserved.
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Quoilin, C., Mouithys-Mickalad, A., Lecart, S., Fontaine-Aupart, M. - P., & Hoebeke, M. (2014). Evidence of oxidative stress and mitochondrial respiratory chain dysfunction in an in vitro model of sepsis-induced kidney injury. BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, 1837(10), 1790–1800.
Résumé: To investigate the role of oxidative stress and/or mitochondrial impairment in the occurrence of acute kidney injury (AKI) during sepsis, we developed a sepsis-induced in vitro model using proximal tubular epithelial cells exposed to a bacteria] endotoxin (lipopolysaccharide, LPS). This investigation has provided key features on the relationship between oxidative stress and mitochondrial respiratory chain activity defects. LPS treatment resulted in an increase in the expression of inducible nitric oxide synthase (iNOS) and NADPH oxidase 4 (NOX-4), suggesting the cytosolic overexpression of nitric oxide and superoxide anion, the primary reactive nitrogen species (RNS) and reactive oxygen species (ROS). This oxidant state seemed to interrupt mitochondrial oxidative phosphorylation by reducing cytochrome c oxidase activity. As a consequence, disruptions in the electron transport and the proton pumping across the mitochondrial inner membrane occurred, leading to a decrease of the mitochondrial membrane potential, a release of apoptotic-inducing factors and a depletion of adenosine triphosphate. Interestingly, after being targeted by RNS and ROS, mitochondria became in turn producer of ROS, thus contributing to increase the mitochondrial dysfunction. The role of oxidants in mitochondrial dysfunction was further confirmed by the use of iNOS inhibitors or antioxidants that preserve cytochrome c oxidase activity and prevent mitochondria] membrane potential dissipation. These results suggest that sepsis-induced AKI should not only be regarded as failure of energy status but also as an integrated response, including transcriptional events, ROS signaling, mitochondrial activity and metabolic orientation such as apoptosis. (C) 2014 Elsevier B.V. All rights reserved.
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Ralay-Ranaivo, B., Desmaele, D., Bianchini, E. P., Lepeltier, E., Bourgaux, C., Borgel, D., Pouget, T., Tranchant, J. F., Couvreur, P., & Gref, R. (2014). Novel self assembling nanoparticles for the oral administration of fondaparinux: Synthesis, characterization and in vivo evaluation. Journal Of Controlled Release, 194, 323–331.
Résumé: Fondaparinux (Fpx) is the anticoagulant of choice in the treatment of short- and medium-term thromboembolic disease. To overcome the low oral bioavailability of Fpx, a new nanoparticulate carrier has been developed. The nanoparticles (NPs) contain squalenyl derivatives, known for their excellent oral bioavailability. They spontaneously self-assemble upon both electrostatic and hydrophobic interactions between the polyanionic Fpx and cationic squalenyl (CSq) derivatives. The preparation conditions were optimized to obtain monodisperse, stable NPs with a mean diameter in the range of 150-200 nm. The encapsulation efficiencies were around 80%. Fpx loadings reached 39 wt.%. According to structural and morphological analysis, Fpx and CSq organized in spherical multilamellar (“onion-type”) nanoparticles. Furthermore, in vivo studies in rats suggested that Fpx was well absorbed from the orally administered NPs, which totally dissociated when reaching the blood stream, leading to the release of free Fpx. The Fpx: CSq NPs improved the plasmatic concentration of Fpx in a dose-dependent manner. However, the oral bioavailability of these new NPs remained low (around 0.3%) but of note, the C-max obtained after oral administration of 50 mg/kg NPs was close to the prophylactic plasma concentration needed to treat venous thromboembolism. Moreover, the oral bioavailability of Fpx could be dramatically increased up to 9% by including the nanoparticles into gastroresistant capsules. This study opens up new perspectives for the oral administration of Fpx and paves the way towards elaborating squalene-based NPs which self assemble without the need of covalently grafting the drug to Sq. (C) 2014 The Authors. Published by Elsevier B.V.
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Rampazzo, E., Bonacchi, S., Genovese, D., Juris, R., Montalti, M., Paterlini, V., Zaccheroni, N., Dumas-Verdes, C., Clavier, G., Meallet-Renault, R., & Prodi, L. (2014). Pluronic-Silica (PluS) Nanoparticles Doped with Multiple Dyes Featuring Complete Energy Transfer. Journal Of Physical Chemistry C, 118(17), 9261–9267.
Résumé: We report here the design of two sets Of multifltiorophoric silica nanoparticles, observing unprecedented efficiencies in the energy-transfer processes among the doping dyes. These nanomaterials show a very high overall sensitization, allowing under a single wavelength excitation to obtain many different colors (one per nanoparticle) in emission with negligible crosstalk. Moreover, each particle can present very large and tunable pseudo-Stokes shifts (up to 435 nm), a very high brightness even exciting the bluest donor, and a negligible residual emission intensity from all donor dyes. All these features, combined with colloidal stability and synthetic method reliability, make these multicomponent nanoparticles very promising for multiplex analysis and for all the diagnostic techniques requiring high sensitivity associated with a large Stokes shift.
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Rogez, B., Yang, H., Le Moal, E., Lévêque-Fort, S., Boer-Duchemin, E., Yao, F., Lee, Y. - H., Zhang, Y., Wegner, D., Hildebrandt, N., Mayne, A. J., & Dujardin G. (2014). Fluorescence lifetime and blinking of individual semiconductor nanocrystals on graphene. J. Phys. Chem. C, 118, 18445–18452.
Résumé: A new class of optoelectronic nanodevices consisting of 0D semiconductor nanocrystals and 2D single graphene layers is attracting much attention. In particular, such a system may be used to investigate and control the transfer of energy and charge in low-dimensional systems. To this end, the fluorescence dynamics of individual colloidal quantum dots(QDs) on graphene are investigated on both the 10−9 to 10−8 s time scale (fluorescence lifetime) and the 1−100 s time scale(blinking statistics) in this paper. We find that (i) a nonradiative energy transfer rate of ≈5 × 10+8 s−1 is obtained from the reduced lifetimes of QDs on graphene as opposed to those on insulating substrates such as glass; (ii) QDs still exhibit fluorescence intermittency (“blinking”) on graphene; (iii) the cumulative distribution functions of the “off” times may be described by power-law statistics; (iv) QD coupling to graphene increases the time spent in the “on” state while the time spent in the “off” state remains relatively unchanged; and (v) the fluorescence emission spectrum of the QDs is practically unaltered by the QD−graphene coupling.
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Sancey, L., Lux, F., Kotb, S., Roux, S., Dufort, S., Bianchi, A., Cremillieux, Y., Fries, P., Coll, J. - L., Rodriguez-Lafrasse, C., Janier, M., Dutreix, M., Barberi-Heyob, M., Boschetti, F., Denat, F., Louis, C., Porcel, E., Lacombe, S., Le Duc, G., Deutsch, E., Perfettini, J. - L., Detappe, A., Verry, C., Berbeco, R., Butterworth, K. T., McMahon, S. J., Prise, K. M., Perriat, P., & Tillement, O. (2014). The use of theranostic gadolinium-based nanoprobes to improve radiotherapy efficacy. The British journal of radiology, 87(1041).
Résumé: A new efficient type of gadolinium-based theranostic agent (AGuIX) has recently been developed for MRI-guided radiotherapy (RT). These new particles consist of a polysiloxane network surrounded by a number of gadolinium chelates, usually 10. Owing to their small size (<5nm), AGuIX typically exhibit biodistributions that are almost ideal for diagnostic and therapeutic purposes. For example, although a significant proportion of these particles accumulate in tumours, the remainder is rapidly eliminated by the renal route. In addition, in the absence of irradiation, the nanoparticles are well tolerated even at very high dose (10 times more than the dose used for mouse treatment). AGuIX particles have been proven to act as efficient radiosensitizers in a large variety of experimental in vitro scenarios, including different radioresistant cell lines, irradiation energies and radiation sources (sensitizing enhancement ratio ranging from 1.1 to 2.5). Pre-clinical studies have also demonstrated the impact of these particles on different heterotopic and orthotopic tumours, with both intratumoural or intravenous injection routes. A significant therapeutical effect has been observed in all contexts. Furthermore, MRI monitoring was proven to efficiently aid in determining a RT protocol and assessing tumour evolution following treatment. The usual theoretical models, based on energy attenuation and macroscopic dose enhancement, cannot account for all the results that have been obtained. Only theoretical models, which take into account the Auger electron cascades that occur between the different atoms constituting the particle and the related high radical concentrations in the vicinity of the particle, provide an explanation for the complex cell damage and death observed.
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Sivankutty, S., Barroca, T., Mayet, C., Dupuis, G., Fort, E., & Leveque-Fort, S. (2014). Confocal supercritical angle microscopy for cell membrane imaging. Opt Lett, 39(3), 555–558.
Résumé: We demonstrate subwavelength sectioning on biological samples with a conventional confocal microscope. This optical sectioning is achieved by the phenomenon of supercritical angle fluorescence, wherein only a fluorophore next to the interface of a refractive index discontinuity can emit propagating components of radiation into the so-called forbidden angles. The simplicity of this technique allows it to be integrated with a high numerical aperture confocal scanning microscope by only a simple modification on the detection channel. Confocal-supercritical angular fluorescence microscopy would be a powerful tool to achieve high-resolution surface imaging, especially for membrane imaging in biological samples.
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Štefančíková L., P. E., Eustache P., Li S., Salado D., Marco S., Guerquin-Kern J.L., Réfrégiers M., Tillement O., Lux F., and Lacombe S. (2014). Cell localisation of gadolinium-based nanoparticles and related radiosensitising efficacy in glioblastoma cells. Cancer Nanotechnology. Cancer Nanotechnology, 5(1), 6.
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Monographies |
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Physique nucléaire: Des quarks aux applications. (2014). Le Sech C. et Ngô C..
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Chapitres de Livres |
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Le Sech, C. (2014). Quantum Confinement Study of the H2+ Ion and H2 Molecule with Monte Carlo Method. In Electronic Structure of Quantum Confined Atoms and Molecules Sen, K. D., Ed.; Springer: Cham, Switzerland (227).
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