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A semi-heterogeneous photocatalytic system was assembled through encapsulation of a lipophilic porphyrin in stabilized polydiacetylene micelles. The colloidal nanohybrid catalyst was valorized in the aerobic photo-oxidation of sulfides to the corresponding sulfoxides. Micelles behaved as nanoreactors by creating a favorable environment for the photo-activation of oxygen nearby thioethers and subsequent sulfoxidation. The process operates selectively under visible light and air atmosphere, with low catalytic loading and in water as the only solvent.
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We report the synthesis of biocompatible perfluorinated micelles designed to improve radiotherapeutic efficacy in a radioresistant tumor environment. In vitro and in vivo behaviors of perfluorinated micelles were assessed at both cellular and tissular levels. The micellar platform offers key advantages as theranostic tool: (i) small size, allowing deep tissue penetration; (ii) oxygen transport to hypoxic tissues; (iii) negligible toxicity in the absence of ionizing radiation; (iv) internalization into cancer cells; (v) potent radiosensitizing effect; and (vi) excellent tumor-targeting properties, as monitored by positron emission tomography. We have demonstrated strong in vitro radiosensitizing effects of the micelle and in vivo tumor targeting, making this nanometric carrier a promising tool for the potentiation of focused radiotherapy.
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Micelas , Tomografía de Emisión de Positrones , Fármacos Sensibilizantes a Radiaciones , Nanomedicina Teranóstica , Animales , Humanos , Fármacos Sensibilizantes a Radiaciones/química , Fármacos Sensibilizantes a Radiaciones/farmacología , Fármacos Sensibilizantes a Radiaciones/síntesis química , Ratones , Línea Celular Tumoral , Fluorocarburos/química , Fluorocarburos/farmacología , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Neoplasias/patologíaRESUMEN
Curcumin is a key constituent of turmeric with a variety of biological activities. From a chemical point of view, curcumin contains different functional groups that can undergo multiple transformations such as Michael addition, cycloaddition, click reaction, polymerisation, etc. Among these, Michael-type reactions under benign conditions constitute a captivating domain of curcumin's reactivity. To the best of our knowledge, no review focusing on the Michael donor-acceptor reactivity of curcumins has been published to date. Herein, we have compiled the chemistry of curcumins with respect to their chemical synthesis, biosynthesis, and involvement in chemical transformations, especially in Michael additions with advances in mechanistic aspects and understanding.
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We report the design, synthesis, and in vitro evaluation of stimuli-responsive nanoscale micelles that can be activated by light to induce a cytotoxic effect. Micelles were assembled from amphiphilic units made of a photoactivatable ferrocenyl linker, connected on one side to a lipophilic chain, and on the other side to a hydrophilic pegylated chain. In vitro experiments indicated that pristine micelles ("off" state) were nontoxic to MCF-7 cancer cells, even at high concentrations, but became potent upon photoactivation ("on" state). The illumination process led to the dissociation of the micelles and the concomitant release of iron species, triggering cytotoxicity.
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Antineoplásicos , Compuestos Ferrosos , Micelas , Metalocenos/farmacología , FototerapiaRESUMEN
We report the development of compact and stabilized micelles incorporating a synthetic LXR agonist prodrug for the passive targeting of atherosclerotic lesions and therapeutic intervention. In vivo studies showed that the nanohybrid micelles exhibited favorable pharmacokinetics/biodistribution and were able to upregulate, to some extent, LXR target genes with no alteration of lipid metabolism.
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Aterosclerosis , Micelas , Humanos , Receptores X del Hígado/uso terapéutico , Distribución Tisular , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/patologíaRESUMEN
Tumor-specific drug delivery is a major challenge for the pharmaceutical industry. Nanocarrier systems have been widely investigated to increase and control drug delivery to the heterogeneous tumor microenvironment. Classically, the uptake of nanocarriers by solid tumor tissues is mainly mediated by the enhanced permeability and retention effect (EPR). This EPR effect depends on the tumor type, its location, the physicochemical properties of the carriers, and the blood perfusion of the tumoral lesions. The main goal of this study was to evaluate in vivo tumor uptake of micelle carriers, assisted by microbubble/ultrasound sonoporation. Micelles were tracked using bi-modal imaging techniques to precisely localize both the nanocarrier and its payload. Micelles were loaded with a near infrared fluorophore and radiolabeled with zirconium-89. Their pharmacokinetics, biodistribution and passive tumor targeting properties were evaluated in a subcutaneous glioblastoma (U-87 MG) mouse model using optical and PET imaging. Finally, accumulation and diffusion into the tumor micro-environment was investigated under microbubble-assisted sonoporation, which helped homogenize the delivery of the micelles. The in vivo experiments showed a good correlation between optical and PET images and demonstrated the stability of the micelles in biological media, their high and long-term retention in the tumors and their clearance through the hepato-biliary pathway. This study demonstrates that bi-modal imaging techniques are powerful tools for the development of new nanocarriers and that sonoporation is a promising method to homogenize nanomedicine delivery to tumors.
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Glioma , Micelas , Ratones , Animales , Distribución Tisular , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos/métodos , Glioma/diagnóstico por imagen , Tomografía de Emisión de Positrones , Portadores de Fármacos/química , Microambiente TumoralRESUMEN
Titanium dioxide nanoparticles were combined with carbon nanotubes and gold to develop improved photocatalysts for the production of hydrogen from water. The entangled nature of the nanotubes allowed for the integration of the photoactive hybrid catalyst, as a packed-bed, in a microfluidic photoreactor, and the chips were studied in the photocatalyzed continuous flow production of hydrogen. The combination of titanium dioxide with carbon nanotubes and gold significantly improved hydrogen production due to a synergistic effect between the multi-component system and the stabilization of the active catalytic species. The titanium dioxide/carbon nanotubes/gold system permitted a 2.5-fold increase in hydrogen production, compared to that of titanium dioxide/carbon nanotubes, and a 20-fold increase, compared to that of titanium dioxide.
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A heterogeneous catalyst consisting of bimetallic rhodium-ruthenium particles immobilized on carbon nanotubes was used in the hydroboration reaction and proved highly effective for a variety of alkenes and alkynes. The reactions were carried out with low catalytic loadings (0.04 mol%), under solvent-free conditions, and at room temperature. In addition, to demonstrate its recyclability, the catalyst was recovered by a simple centrifugation process and reused over 5 consecutive cycles without losing any activity.
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Ethylene glycol can be reliably produced by mild hydrogenation of dimethyl oxalate.
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A carbon nanotube-based packed-bed microreactor was developed for the on-chip oxidation of silanes. The process is catalyzed by a heterogeneous gold-carbon nanotube hybrid that was embedded in the device using a micrometric restriction zone. Integration of the nanohybrid permitted efficient flow aerobic oxidation of the substrates into the corresponding silanols with high selectivity and under sustainable conditions.
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Nanopartículas del Metal , Nanotubos de Carbono , Oro , Microfluídica , Oxidación-ReducciónRESUMEN
Integration of efficient platinum-group-metal (PGM)-free catalysts to fuel cells and electrolyzers is a prerequisite to their large-scale deployment. Here, we describe the development of a molecular-based anode for the hydrogen oxidation reaction (HOR) through noncovalent integration of a DuBois type Ni bioinspired molecular catalyst at the surface of a carbon nanotube modified gas diffusion layer. This mild immobilization strategy enabled us to gain high control over the loading in catalytic sites. Additionally, through the adjustment of the hydration level of the active layer, a new record current density of 214 ± 20 mA cm-2 could be reached at 0.4 V vs RHE with the PGM-free anode, at 25 °C. Near industrially relevant current densities were obtained at 55 °C with 150 ± 20 and 395 ± 30 mA cm-2 at 0.1 and 0.4 V overpotentials, respectively. These results further demonstrate the relevance of such molecular approaches for the development of electrocatalytic platforms for energy conversion.
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We describe herein the assembly and in vivo evaluation of a tailor-made micellar carrier system designed for the optimized encapsulation of a superfluorinated MRI probe and further targeting of solid tumors. The in vivo validation was carried out on MC38 tumor-bearing mice which allowed the confirmation of the efficient targeting properties of the nano-carrier, as monitored by 19F-MRI.
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Imagen por Resonancia Magnética con Fluor-19 , Neoplasias , Animales , Imagen por Resonancia Magnética , Ratones , MicelasRESUMEN
Research on the decontamination of the chemical warfare agent sulfur mustard pursues several objectives that include the neutralization of spared ammunition, the cleaning of affected areas, and also the development of protective equipment or tools. Neutralization of vesicant sulfur mustard involves different chemical routes such as hydrolysis, dehydrochlorination, oxidation, or complete mineralization. This review weighs the pros and cons associated with the different systems reported in the literature, with an emphasis on catalytic procedures, to selectively convert sulfur mustard or its simulants into harmless products.
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The understanding of the cellular uptake and the intracellular fate of nanoparticles and their subsequent influence on cell viability is challenging as far as micelles are concerned. Such systems are dynamic by nature, existing as unimers under their critical micelle concentration (CMC), and as micelles in equilibrium with unimers above the CMC, making canonical dose-response relationships difficult to establish. The purpose of this study was to investigate the in vitro cytotoxicity and uptake of two micellar sytems that are relevant for drug delivery. The two micelles incorporate a poly(ethylene glycol) coating and a pentacosadiynoic core which is either polymerized (pDA-PEG micelles) or non-polymerized (DA-PEG micelles), with the aim of evaluating the influence of the micelles status ("particle-like" or "dynamic", respectively) on their toxicological profile. Intracellular distribution and cytotoxicity of polymerized and non-polymerized micelles were investigated on RAW 264.7 macrophages in order to compare any different interactions with cells. Non-polymerized micelles showed significantly higher cytotoxicity than polymerized micelles, especially in terms of cell permeabilization, correlated to a higher accumulation in cell membranes. Other potential toxicity endpoints of polymerized micelles were then thoroughly studied in order to assess possible responses resulting from their endocytosis. No specific mechanisms of cytotoxicity were observed, neither in terms of apoptosis induction, cell membrane damage, release of inflammatory mediators nor genotoxicity. These data indicate that non-polymerized micelles accumulate in the cell membrane and induce cell membrane permeabilization, resulting in significant toxicity, whereas polymerized, stable micelles are internalized by cells but exert no or very low toxicity.
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Micelas , Polímero Poliacetilénico/toxicidad , Animales , Apoptosis , Portadores de Fármacos , Endocitosis , Inflamación , L-Lactato Deshidrogenasa/metabolismo , Lipopolisacáridos , Ratones , Mitocondrias/metabolismo , Nanopartículas/química , Nanopartículas/toxicidad , Nanoestructuras , Necrosis , Permeabilidad , Polímero Poliacetilénico/química , Polietilenglicoles/química , Polimerizacion , Células RAW 264.7RESUMEN
Micelle-forming amphiphilic drug conjugates were synthesized starting from a biologically active epipodophyllotoxin derivative which was covalently inserted in between a hydrophilic targeting spermine unit, and a hydrophobic stearyl chain. The amphiphilic drug conjugates were further assembled into the corresponding micelles and evaluated in vitro for the active targeting of tumor cells overexpressing the polyamine transport system.
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Micelas , Nanoestructuras , Podofilotoxina/química , Poliaminas/metabolismo , Transporte Biológico , Sistemas de Liberación de Medicamentos , Interacciones Hidrofóbicas e HidrofílicasRESUMEN
Micelle-forming amphiphilic drug conjugates were synthesized starting from a biologically active epipodophyllotoxin derivative which was covalently inserted in between a hydrophilic PEG unit and a hydrophobic stearyl chain. The epipodophyllotoxin-containing amphiphiles were assembled into the corresponding micelles which were evaluated in vivo for their tumor targeting properties.
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Portadores de Fármacos , Micelas , Nanopartículas/química , Podofilotoxina/química , Animales , Línea Celular Tumoral , Humanos , Ratones , Ratones Desnudos , Neoplasias/diagnóstico por imagen , Polietilenglicoles/química , Espectroscopía Infrarroja Corta , Trasplante HeterólogoRESUMEN
In this study, a "click and hybridization" strategy was developed for the functionalization of polydiacetylene micelles with a targeting aptamer ligand. Decoration of the nanocarriers with an anti-Annexin A2 sequence efficiently triggered enhanced internalization of the functionalized micelles in the MCF-7 cell line, with a marked increase compared to control micelles.
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Anexina A2/genética , Aptámeros de Nucleótidos/administración & dosificación , Portadores de Fármacos/administración & dosificación , Micelas , Polímero Poliacetilénico/administración & dosificación , Transporte Biológico , Humanos , Células MCF-7RESUMEN
A bioorthogonal approach is explored to release the content of nanoparticles on demand. Exploiting our recently described click-and-release technology, we developed a new generation of cleavable micelles able to disassemble through a sequential enzymatic and bioorthogonal activation process. Proof-of-concept experiments showed that this new approach could be successfully used to deliver the substances encapsulated into micelles in living cells as well as in mice by two complementary targeted strategies.
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Micelas , Preparaciones Farmacéuticas/metabolismo , Alquinos/química , Animales , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Química Clic , Ciclooctanos/química , Liberación de Fármacos , Glucurónidos/química , Humanos , Cinética , Ratones , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Preparaciones Farmacéuticas/química , Tetrazoles/química , Trasplante HeterólogoRESUMEN
Gold nanoparticles supported on carbon nanotubes were shown to efficiently catalyze the oxidation of alcohols to methyl esters under mild and selective reaction conditions. The reaction works with low catalyst loadings and the nanohybrid could be readily recycled and reused.
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Polydiacetylene micelles were assembled from four different cationic amphiphiles and photopolymerized to reinforce their architecture. The produced micelles were systematically investigated, in interaction with siRNAs, for intracellular delivery of the silencing nucleic acids. The performances of the carrier systems were rationalized based on the cell penetrating properties of the micelles and the nature of their cationic complexing group, responsible for efficient siRNA binding and further endosomal escape.