1,721,116 research outputs found
Fluorescent self-assembled micellar nanometers for the evaluation of lipophilicity and acidity of fatty acids, penicillins and non-steroidal anti-inflammatory drugs
No full textEvaluation and parametrization of lipophilicity is an important step in profiling drug-like properties of new molecules for their pharmaceutical use, in particular as regards oral absorption and brain uptake. We have studied an approach in which micelles behave as nanocontainers promoting the self-assembly of multicomponent molecular devices. These devices exist exclusively inside the nanosized and poorly hydrated micellar core, and are capable of measuring molecular lipophilicity by means of a fluorescent signal. The variation of fluorescence intensity is proportional to the capability of a given molecule to penetrate the palisade layer of a micelle and to reach the hydrophobic core, as once it is inside the nanocontainer it competes with a receptor-fluorescent substrate assembly. In turn, this molecular ability is directly related to its lipophilicity.
Our micellar nanometers represent an advancement with respect to traditional lipophilicity evaluation methods, as micelles can mimic the natural bi-layer of cellular membranes. Moreover, being systems working in water, they allow to directly compare the effective lipophilicity of a chosen series of molecules under real-world, in vivo conditions, e.g. as regards working pH, concentration of electrolites, solution background, temperature.
The effective values inside a membrane-like environment of chemical-physical parameters (e.g. the pKa of the acid fragment of a large molecule) can also be evaluated in parallel. Changing the contained fluorescent assembly or the micellar nanocontainer, the lipophilicity of different series of molecules can be parametrized, as we have demonstrated by stepping from linear fatty acids[1] and bicarboxylic acids, to penicillins and non-steroidal anti-inflammatory drug
Self-Assembled monolayers of thiols on grafted silver-nanoparticles: controlling surface coverage at the nanoscale
No full textA thermodynamic scale for lipophilicity: evaluating micelle-water distribution of mono- and di-carboxylates under physiological pH condition
No full textMolecular Self-Assembled Monolayers on NanoParticles Self-Assembled Monolayers: an easy optical method to calculate coating from molecular mxtures
No full textmonolayers of thiolatyed dye are obtained on monolayers of silver nanoparticles on glass. A method based on absorption spectra is presented, to determine the surface composition from the composition of the coating solution, in the case of mixed thiol
Self-assembled fluorescent micellar devices for measuring the lipophilicity of drugs
No full textMicellar devices contain a lipophilic complex and a fluorescent ligand for the apical position of the metal complexes. Addition of competing lipophilic molecules results in the displacement of the fluorescent ligand from the metal centre and in a change in fluorescent intensity that is proportional to the lipophilicity of the added molecul
Gold nanostars co-coated with the Cu(II) complex of a tetraazamacrocyclic ligand
No full textThe twelve-membered tetraazamacrocyclic ligand L1 bears an appended lipoic acid unit, whose disulphide
ring is an efficient grafting moiety for the surface of gold nanostars (GNS). The GNS that were
used featured a localized surface plasmon resonance (LSPR) absorption at ∼800 nm, i.e. in the near infrared
(NIR). We investigated different approaches for coating them with the Cu2+ complex of L1. While the
direct reaction of [CuL1]2+ with as-prepared GNS led to aggregation, an initial coating step with polyethyleneglycol–
thiol (PEG–SH) was found to be advantageous. Displacement reactions were carried out on
pegylated GNS either with [CuL1]2+, directly generating [Cun(L1@GNS)]2n+, or with void L1, thus obtaining
L1@GNS that coordinates Cu2+ in a second step. In both cases, even with a large excess of the competing
disulphide moiety, only partial displacement of PEG–SH is observed, obtaining ca. 500–1500 [CuL1]2+
per GNS depending on the conditions, with PEG–SH remaining in the [Cun(L1@GNS)]2n+ hybrids and
imparting them with remarkable stability. Comparison of the photothermal and two-photon luminescence
(TPL) properties of the GNS between the pegylated GNS and [Cun(L1@GNS)]2n+ revealed that the grafted
copper complex does not change them to any extent. Finally, the stability against demetallation and transmetallation
of the complexes, as well as the fast kinetics of complexation of the monodispersed macrocycle
and of L1@GNS, have been examined, suggesting [Cun(L1@GNS)]2n+ as a device capable of TPL
optical tracking and NIR photothermal therapy and as a possible agent for PET imaging
Optical Method for Predicting the Composition of Self-Assembled Mono layers of Mixed Thiols on Surfaces Coated with Silver Nanoparticles
Full text linkWith a simple optical method, based on UV-vis absorption spectra on glass slides, it is possible to predict the composition of self-assembled monolayers of mixed thiols, grafted on monolayers of silver nanoparticles. Glass slides are modified with the layer-by-layer technique, first forming a monolayer of mercaptopropyltrimethoxysilane, then grafting a monolayer of silver nanoparticles on it. These surfaces are further coated by single or mixed thiol monolayers, by dipping the slides in toluene solutions of the chosen thiols. Exchange constants are calculated for the competitive deposition between the colorless 1-dodecanethiol or PEG5000 thiol and BDP-SH, with the latter being a thiol-bearing molecule containing the strongly absorbing BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) moiety, synthesized on purpose. The constants are calculated by determining the fraction of BDP-SH deposited on the surface from a solution with a given molar fraction, directly measuring the absorption spectra of BDP-SH on the slides. Then, the exchange constant for the competitive deposition between 1-dodecanethiol and PEG5000 thiol is calculated by combining their exchange constants with BDP-SH. This allows to predict the fraction of the two colorless thiols coating the silver nanoparticles slides obtained from a toluene solution with a given molar fraction, for example, of PEG5000 thiol. The correctness of the calculated surface fraction is verified by studying the coating competition between 1-dodecanethiol and a PEG5000 thiol remotely modified with a strongly absorbing fluorescein fragmen
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Synthesis of multifunctionnal gold nanoparticles for image guided therapy
No full textAfin d'améliorer la sélectivité de la radiothérapie dans le cadre du traitement de certains cancers, nous proposons l'utilisation de nanoparticules radiosensibilisantes fonctionnalisées pour le suivi par imagerie médicale. Ces objets, constitués d'un coeur d'or recouvert d'une couche organique, permettent de combiner imagerie multimodale et activité thérapeutique télécommandée, ouvrant ainsi la voie vers la thérapie guidée par imagerie. L'effet radiosensibilisant pourra être généré au moment opportun, déterminé à partir de l'imagerie. L'étude de biodistribution par imagerie TEMP/CT chez des souris a montré une libre circulation des nanoparticules et une élimination rénale avec une présence modérée des nanoparticules dans le foie qui n'est, cependant, pas due à un phénomène d'opsonisation. L'étude par 1RM du cerveau de rats portant un gliosarcome a indiqué une accumulation significative des nanoparticules Au@TADOTAGA-Ge au sein de la tumeur. Enfin le co-marquage des nanoparticules d'or par Gcr et 64Cu2+ (complexées par les ligands macrocycliques) a permis de suivre ces objets, chez le même animal, après injection intraveineuse, à la Ibis par TEP et 1RM dont la combinaison bien que très recherchée est rarement mise en oeuvre. Le caractère radiosensibilisant de la suspension de nanoparticule Au@TADOTAGA a été confirmé par le suivi de croissance tumorale après traitement par irradiation MRT 15 minutes après l'injection des nanoparticules par voie intratumorale. Le gain thérapeutique de la mise en oeuvre de ce traitement a ensuite été validé par une irradiation MR'F 24 heures après l'injection intraveineuse des nanoparticules à des rats portant un gliosarcome.The original properties of nanoparticles make them extremely attractive in the field of oncology. In fast, gold nanoparticles coated by macrocyclic ligands allow imaging and therapy with only one object. Therefore, multifunctional platforms are very promising for image-guided therapy, winch constitutes an important step towards personalization of treatment. This consists of stimulating the therapeutic activity of the nanoparticles when their accumulation is high within the tumor zone and low in healthy tissues. A higher selectivity of the treatment is therefore expected. Biodistribution study by SPECT/CT has shown free circulation, renal elimination and a moderate retention by the liver of the nanoparticles. However, this retention is not due to the opsonisation processus. The MRI study of rats' brain carrying a gliosarcoma has shown an accumulation of nanoparticles Au@FADOTAGA-Gd in the tumor. Moreover, the co-labeling of these nanoparticles by Ge and 64Cts2+was successfully performed. As a result, PET/MRI images, a much researched combination but rarely achieved, were acquired on the same animal alter intravenous injection of the co-labeled nanoparticles. The radiosensitizing character of nanoparticles Au@TADOTAGA was confirmed by the follow up of tumor growth alter a treatment by MRT (microbeam irradiation) 15 minutes after intratumoral injection of nanoparticles. The therapeutic gain of this treatment has been validated by MRT 24 hours after intravenous injection of nanoparticles to rats carrying gliosarcoma (radioresistant tumor in radiosensitive organ)
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