16 research outputs found

    Metal-bis(dithiolene) complexes for cancer theranostics : photothermal therapy, photocontrolled drug delivery and photoacoustic properties

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    Ce travail s’intéresse à l’exploitation des propriétés photothermiques dans le proche infrarouge (NIR) des complexes de métal-bis(dithiolène) neutres pour des applications biomédicales. L’encapsulation de ces complexes dans des nanoparticules polymère ou dans des liposomes thermosensibles a permis de mettre à profit leur effet photothermique remarquable pour la théranostique du cancer. En effet, ces travaux de thèse démontrent que les vecteurs photoactivables formulés présentent un fort potentiel pour une utilisation comme agents photosensibilisateurs pour la thérapie photothermique. De plus, l’irradiation laser du complexe encapsulé permet de moduler la perméabilité du vecteur et ainsi de libérer un agent co-encapsulé avec un bon contrôle spatio-temporel. Ces travaux démontrent également que l’effet photothermique des complexes de métalbis(dithiolène) peut être mis à profit dans la conception d’agent de contraste pour l’imagerie photoacoustique. Finalement, ce travail s’est concentré sur l’étude et la comparaison des propriétés photothermiques de sept agents moléculaires. Les résultats de cette étude font clairement apparaître que les performances remarquables des complexes bis(dithiolènes), couplées à leurs excellente stabilité photochimique et thermique, en font des candidats très prometteurs pour la théranostique du cancer.This work focuses on the exploitation of the photothermal properties in the near-infrared (NIR) region of neutral metal-bis(dithiolene) complexes for biomedical applications. Encapsulation of these complexes in polymer nanoparticles or in thermosensitive liposomes allowed to use theirremarkable photothermal effect for cancer theranostics. This work demonstrates that theformulated photoactive nanovectors have great potential to be used as photosensitizers forphotothermal therapy. Moreover, laser irradiation of the encapsulated complex allowed to finely tune the permeability of the cargo, thus leading to the release of the co-encapsulated agent with a high spatiotemporal control. This work also demonstrates that the photothermal effect of metal-bis(dithiolene) complexes can be used for designing the design of contrast agents for photoacoustic imaging. Finally, this work focused on the study and the comparison of the phtotothermal properties of seven molecular agents. The results of this study clearly show that the remarkables properties of metal-bis(dithiolene) complexes, coupled with their excellent photochemical and thermal stability, make them very promising candidates for cancer theranostics

    Laser triggered phase transition in photothermal liquid crystals

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    International audienceReversible high temperature phase transitions were easily induced under laser irradiation in pure thermotropic liquid crystals built around photothermal nickel-bis(dithiolene) cores. The strong photothermal activity of nickel-bis(dithiolene) liquid crystalline thin films allows reaching a temperature as high as 250 °C directly from room temperature in a few seconds with high spatial control

    Optimization of a Solid-Phase Extraction Procedure for the Analysis of Drug-Loaded Lipid Nanoparticles and its Application to the Determination of Leakage and Release Profiles

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    International audienceTo understand and predict the efficacy and toxicity of nanoparticle-based drugs in vivo, the free and entrapped forms of the drug have to be determined using suitable characterization methods. Herein, a solid-phase extraction (SPE) method combined with high-performance liquid chromatography (HPLC) measurements were used to separately quantify free and entrapped cyclosporine A (CsA) in 50 and 120 nm-sized lipid nanoparticles (NPs). Combined with colloidal stability measurements, HPLC quantification of the free and entrapped drug, separated using SPE, was used to monitor the stability of the nanotherapeutics under storage or physiological conditions. The SPE method was proven not to alter the core-shell template of the lipid nanocarriers. Method validation demonstrated suitable linearity, repeatability, accuracy, and specificity to quantify the free, entrapped, and total drug. Under storage conditions, the %free and %entrapped CsA remained constant over 9 weeks for both NPs. Under physiological conditions, the release profile was similar for both buffers/mediums used, indicating a biphasic mode of release. The validated SPE method was proven to be suitable for the determination of a wide range of free versus entrapped compounds

    Development and validation of a novel UPLC-ELSD method for the assessment of lipid composition of nanomedicine formulation

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    Lipid nanocarriers incorporating glycerides, polyethylene glycol (PEG)-stearates and phospholipids have attracted great attention for in vivo diagnostic, in vivo imaging, activated or non-activated targeted drug delivery. For quality control purposes, the development of appropriate methods for the quantification of their lipid components is needed. In the present study, we developed an analytical method for lipid quantification in formulated nanoparticles. PEG-stearates and glycerides were analyzed in a single run by RP-UPLC-ELSD using a two-step gradient elution program, while the analysis of phospholipids was accomplished by HILIC-UPLC-ELSD after isolation using an SPE silica column. Using both isolated compounds and commercial lipid standards, calibration curves were produced using second-order polynomials to attain the quantitative evaluation of each lipid excipient. Relative standard deviation of all analytes was between 0.9% and 5.3% for intra-day precision and recovery ranged from 83.5% to 112.2%. The presented method was successfully implemented to study the manufacturing process and stability of the formulated lipid excipients during long-term storage and accelerated conditions. The formulation lipid yield was determined and found equal to 82.5%

    : An Index to Rank Molecular Photothermal Agents

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    International audienceRecently, a large variety of photothermal agents have been developed and are currently under study, owing to their wide range of applications. Nonetheless, a comparison of their relative performances remains a challenge, and it appears that no tool is yet available for rationalizing the data reported in the literature. Indeed, we demonstrate in this paper that neither the temperature increase (Delta T) nor the photothermal efficiency (eta) are sufficient to account for the performance of a photothermal agent. From this observation, we propose that a new index, I-PTmax, could be used, in order to properly rank molecular photothermal agents according to their efficacy for converting light into heat, in a similar fashion that brilliance is used to compare luminescence properties

    David Lasser - An American Spaceflight Pioneer

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    David Lasser was one of the founders of the American Interplanetary Society (later known as the American Rocket Society) and author of the first English-language book (in 1931) on the use of rockets for human spaceflight. His involvement in the fledgling spaceflight movement was short-lived as he moved on to pursue a distinguished, if turbulent, career in the labor movement. In lieu of an oral history, Mr. Lasser provided his recollections on the pioneering days of rocketry and his thoughts on mankind's destiny in space. This paper provides an overview of Mr. Lasser's life and accomplishments as an American spaceflight visionary, along with a compilation of the information that he graciously provided

    Derby LLM : Évaluation comparative des approches RAG et fine-tuning

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    National audienceLes grands modèles de langage ont récemment été largement exploités dans les agents conversationnels, où l’injection de connaissances pour des domaines d’applications spécifiques est un enjeu crucial. Nous comparons deux approches : le fine-tuning et la génération augmentée de récupération. Nous évaluons ces techniques pour deux cas d’usage différents avec des métriques automatiques et la préférence humaine. Bien que la pertinence des réponses soit proche, la fidélité et la préférence humaine avantagent la génération augmentée de récupération

    Derby LLM : Évaluation comparative des approches RAG et fine-tuning

    No full text
    National audienceLes grands modèles de langage ont récemment été largement exploités dans les agents conversationnels, où l’injection de connaissances pour des domaines d’applications spécifiques est un enjeu crucial. Nous comparons deux approches : le fine-tuning et la génération augmentée de récupération. Nous évaluons ces techniques pour deux cas d’usage différents avec des métriques automatiques et la préférence humaine. Bien que la pertinence des réponses soit proche, la fidélité et la préférence humaine avantagent la génération augmentée de récupération

    MTEB-French: Resources for French Sentence Embedding Evaluation and Analysis

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    Recently, numerous embedding models have been made available and widely used for various NLP tasks. The Massive Text Embedding Benchmark (MTEB) has primarily simplified the process of choosing a model that performs well for several tasks in English, but extensions to other languages remain challenging. This is why we expand MTEB to propose the first massive benchmark of sentence embeddings for French. We gather 15 existing datasets in an easy-to-use interface and create three new French datasets for a global evaluation of 8 task categories. We compare 51 carefully selected embedding models on a large scale, conduct comprehensive statistical tests, and analyze the correlation between model performance and many of their characteristics. We find out that even if no model is the best on all tasks, large multilingual models pre-trained on sentence similarity perform exceptionally well. Our work comes with open-source code, new datasets and a public leaderboard

    Development and validation of characterization methods for Lipidots® Multifunctional Platform: a step towards industrial transfer

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    Lipidots® technology has thrived towards a versatile nanodelivery platform for designing and producing a series of nanoproducts for in vivo diagnostic, in vivo imaging, activated or non-activated targeted drug delivery. In order to ensure quality of final products, characterization as nanotherapeutics is a key parameter. Thus, we are seeking to implement and validate a panel of characterization methods significantly suitable for Lipidots®. More particularly, we have investigated the lipid quantification, the drug/dye encapsulation, release kinetics and leakage to anticipate the nanocarrier behavior in biological media
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