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Hardy, John George. "Dendrons for active ingredient formulation". Thesis, University of York, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.437583.
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MARAVAL, VALERIE. "Synthese et applications de dendrons phosphores". Toulouse 3, 2000. http://www.theses.fr/2000TOU30090.
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Les dendrimeres sont des macromolecules arborescentes de structure definie preparees suivant deux voies de synthese : par la methode divergente, la synthese se fait du cur vers la peripherie de la molecule, et par la methode convergente, des fragments dendritiques appeles dendrons sont d'abord prepares puis assembles sur un cur plurifonctionnel. Les travaux presentes dans cette these portent sur l'elaboration de dendrons phosphores par une methode divergente et sur l'etude de leur reactivite. Le premier chapitre est une mise au point bibliographique sur les dendrons. Apres une description des differentes methodes de synthese de ces molecules et de leurs proprietes physicochimiques, la deuxieme partie concerne la preparation d'assemblages macromoleculaires par association de dendrons. Enfin, quelques exemples d'applications de ces molecules sont developpes. Dans le second chapitre, la synthese divergente de dendrons a cur fonctionnalise est decrite, ainsi que l'etude de la reactivite de la fonction vinylique composant le cur de l'un d'eux. Le chapitre iii porte sur l'utilisation du dendron precedemment etudie pour elaborer divers systemes multidendritiques originaux. Ceux-ci sont prepares par association de dendrons sur un metal ou sur un cur plurifonctionnel, ou encore par greffage de plusieurs dendrons sur un dendrimere central. Dans le chapitre iv, le meme dendron est utilise pour preparer des co-gels de silice et l'etude des materiaux formes est decrite. Le chapitre v porte sur la fonctionnalisation de surface de dendrimeres jusqu'a la sixieme generation par des clusters de fer. Enfin, le chapitre vi decrit l'utilisation en catalyse homogene de dendrimeres et de dendrons phosphores portant des complexes metalliques respectivement en surface et au cur. Leur activite catalytique a ete testee dans trois reactions et le probleme de la recuperation et de la reutilisation du catalyseur est egalement aborde.
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Al-Jamal, Khuloud Taysir Yousef. "Studies on cationic hydrophobic dendrons and hydrophilic dendrimers". Thesis, University College London (University of London), 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.414002.
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Preston, Sarah Suzanne. "Metal coordination directed folding of intramolecularly hydrogen-bonded dendrons". Columbus, Ohio : Ohio State University, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1135869971.
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Wyszogrodzka, Monika [Verfasser]. "New bifunctional polyglycerol dendrons for biomedical applications / Monika Wyszogrodzka". Berlin : Freie Universität Berlin, 2009. http://d-nb.info/1023582120/34.
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Preston, Sarah Suzanne. "Metal coordination directed folding of intramolecularly hydrogen-bonded dendrons". The Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=osu1135869971.
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Qiu, Jieru. "Dendrons phosphorés fluorescents amphiphiles : synthèse, caractérisation, applications en oncologie". Thesis, Toulouse 3, 2019. http://www.theses.fr/2019TOU30274.
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Les nanotechnologies ont le grand potentiel de révolutionner des technologies classiques variées, dû au développement de nombreux nanodispositifs et ont été intensément étudiées durant la dernière décade. Parmi les nanoparticules utilisées, les dendrimères et dendrons appartiennent à ce "nano-monde" en vertu de leur taille nanométrique, qui peut être modifiée à volonté, ainsi que par exemple leur multivalence et leurs charges. A l'intérieur de l'espace dendrimère, les dendrimères phosphorés apparaissent comme étant parmi les systèmes dendritiques les plus utiles, grâce à l'extraordinaire réactivité et adaptabilité de la chimie du phosphore. Dans ce mémoire nous décrivons la synthèse de plusieurs familles de dendrons phosphorés fluorescent amphiphiles potentiellement intéressants dans les domaines des nanomatériaux et de la nanomédecine. L'hexachlorocyclotriphosphazene utilisé comme cœur a été substitué par cinq groupements hydroxybenzaldehyde et un monomère tel que le pyrene ou un dérivé maleimide comme entité fluorescente ou l'azabisdimethylphosphonate comme groupement non fluorescent. Ces dendrons ont été préparés jusqu'à la génération 2 selon une voie divergente. La dernière étape a consisté en un greffage d'aminopyrrolidine ou aminopipéridine, suivi par protonation par HCl des groupements amines cycliques terminaux conduisant à la formation de dendrons phosphorés amphiphiles. La caractérisation physico-chimique a été réalisée par tout un ensemble de techniques : RMN, UV, CMC, diffusion dynamique de la lumière, potentiel zéta, microscopie électronique à transmission, fluorescence, dichroïsme circulaire, thermogravimétrie. L'étape suivante a consisté en l'étude des propriétés biologiques. Leur cytotoxicité a été déterminée en utilisant des tests MTT et Alamar Blue, effectués sur onze lignées cancéreuses ou saines (HL-60, HCT-116, A549, MCF7, PC3, U87, K562, K562R, MCR5, MDA-MB231 and HT-29). Des tests d'hémolyse ont été effectués pour tester l'effet des dendrons sur la membrane des cellules. Leur habilité à s'associer à du matériel génétique tels que les petits ARN interférents (siRNA siBCL-xL) a été mise en évidence par des expériences notamment d'électrophorèse sur gel. L'internalisation de ces associations (dendriplexes) dans les cellules tumorales a été suivie par cytométrie en flux. Dans le but de moduler les propriétés anticancéreuses des dendrons fluorescents amphiphiles, des quantum dots de carbone (CQDs) ont été associés avec les dendrons pyrene en présence d'un agent cytotoxique comme la doxorubicine encapsulée dans les micelles formées par les dendron pyrene et les CQDs. [...]Nanotechnologies have the high potential to revolutionize various other classical technologies in many fields, due to the development of numerous nanodevice types, and have been intensively studied over the last decade. Among these nanoparticles, dendrimers and dendrons pertain to the "nano-world" by virtue of their size. Their nanometric sizes can be tailored as well, for instance, their multivalency and charges. Within the dendrimer space, phosphorus dendrimers and dendrons appear to be among the most useful dendritic systems due to the extraordinary reactivity and versatility of the phosphorus chemistry. In this thesis, we designed several families of original amphiphilic fluorescent phosphorus dendrons with interesting potential in the fields of nanomaterials and nanomedicine. Hexachlorocyclotriphosphazene used as a core was linked with five 4-hydroxybenzaldehyde and one monomer (pyrene and maleimide derivatives as fluorescent monomers and azabisdimethylphosphonate derivatives as non-fluorescent monomer). The dendrons were prepared up to generation 2 by a divergent method. The last step is the grafting of amino pyrrolidine or amino piperidine following by protonation with HCl to get the expected cationic amphiphilic fluorescent phosphorus dendrons. Their physical characterization were evaluated through numerous technics: NMR, UV, critical micelle concentration (CMC), dynamic light scattering (DLS), zeta potential, transmission electron microscopy (TEM), fluorescent spectra, circular dichroism and thermogravimetry. In a next step, the biological properties of the dendrons have been examined. The cytotoxicity of dendrons was determined using MTT test and Alamar Blue assay performed on eleven cells lines including both cancer cells and healthy cells (HL-60, HCT-116, A549, MCF7, PC3, U87, K562, K562R, MCR5, MDA-MB231 and HT-29 cells line). Hemolysis assays were used to test the effect of dendrons on the cell membrane. Their ability to bind genetic material was studied by gel electrophoresis using fluorescein-labeled small interference RNA siBCL-xL. Flow cytometry method was used to study the internalization of dendriplexes into tumor cells. In order to modulate the anticancer properties of the fluorescent dendrons, carbon quantum dots (CQDs) were chosen to conjugate with the pyrene dendrons in the presence of a cytotoxic agent like doxorubicin (DOX), physically loaded into 'micelles'. [...]
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Chen, Liang. "Synthèse et applications biologiques de dendrimères et dendrons phosphorés". Thesis, Toulouse 3, 2020. http://www.theses.fr/2020TOU30277.
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L'objectif de ces travaux était de concevoir plusieurs familles de dendrimères phosphorés cationiques et de dendrons neutres et cationiques, et d'étudier leur potentiel dans le domaine de la biologie/nanomédecine. Premièrement, nous avons revisité les dendrimères phosphorés cationiques comme vecteur non viral pour le transport de gènes contre le cancer. L'efficacité d'expression des gènes a été détectée par microscopie à fluorescence, cytométrie en flux, réaction en chaîne de polymérase quantitative en temps réel (rt-qPCR) et tests Western blot. Les résultats révèlent que dans les conditions optimisées, la transfection de l'ADNp induit l'expression significative de la protéine p53 comme montré par l'arrêt du cycle cellulaire résultant (régulation de p21 et de l'expression de Cdk4/Cyclin-D1) et le Western blot. De plus, le potentiel en thérapie génique du cancer des polyplexes a finalement été validé sur un modèle tumoral de xénogreffe après injection intra-tumorale, sans toxicité systémique. Au vu de tous les résultats déjà obtenus, l'utilisation de dendrimères phosphorés cationiques pour la biologie est sans aucun doute très prometteuse pour l'avenir. Deuxièmement, les dendrons phosphorés complexant Cu(II) et Au(III) (génération 1) portant 10 Cu(II)Cl2 ou [Au(III)Cl2]+ à leur surface, et des chaînes alkyle en C11 et C17 ont été synthétisées. Ces dendrons ont montré une activité antiproliférative significative contre les lignées cellulaires cancéreuses telles que 4T1 et MCF-7 (cancer du sein). Les meilleurs résultats concernant l'activité antiproliférative pour tuer les cellules cancéreuses ont été obtenus avec les complexes de dendrons Au(III) portant une courte chaîne alkyle. L'analyse de la voie de mort cellulaire révèle que les complexes de dendrons pourraient modifier l'état des protéines liées au cycle cellulaire et à l'apoptose, entraînant un arrêt de la phase S du cycle cellulaire et une apoptose. En particulier, les complexes de Au(III) ont induit une létalité cellulaire dépendante de la caspase, en favorisant la translocation de Bax vers les mitochondries et la libération de Cyto C, tandis que les complexes de Cu(II) sont de faibles activateurs de la caspase-3, en lien avec leur activité antiproliférative modérée dans les cellules cancéreuses. Ses études dans leur ensemble ont montré que ces complexes de dendrons phosphorés originaux représentent une nouvelle classe de nano-médicaments anticancéreux, et leur développement ouvrira de nouvelles voies pour lutter contre les cancers. Enfin, nous avons préparé le dendron phosphoré amphiphile 1-C12G1 portant une longue chaîne alkyle linéaire (C12H25), et dix groupes pyrrolidine protonés en surface. Le 1-C12G1 forme des nanomicelles qui permettent d'encapsuler le médicament anticancéreux DOX et de complexer l'inhibiteur miR-21. [...]The aim of this work was to design several families of cationic phosphorus dendrimers and of neutral and cationic dendrons, and to investigate their potential in the field of biology/nanomedicine. Firstly, we revisited the cationic phosphorus dendrimers as a non-viral vector for gene delivery towards cancer therapy. The expression efficiency of genes was detected by fluorescence microscopy, flow cytometry, quantitative real time polymerase chain reaction (rt-qPCR) and Western blot assays. The results reveal that under the optimized conditions, the transfection of pDNA induces the significant p53 protein expression as verified through the resulting cell cycle arrest (regulation of p21 and Cdk4/Cyclin-D1 expression) and Western blotting. Moreover, the cancer gene therapy potential of the polyplexes was finally validated through therapy of a xenografted tumor model after intra-tumoral injection without systemic toxicity. In view of all the results already obtained, undoubtedly the use of cationic phosphorus dendrimers for biology holds great promises for the future. Secondly, the first-in-class Cu(II) and Au(III) metaled phosphorus dendrons (generation 1) bearing 10 Cu(II)Cl2 or [Au(III)Cl2]+ on their surface, and with C11 and C17 linear alkyl chains were synthesized. These dendrons showed significant antiproliferative activity against cancer cell lines such as 4T1 and MCF-7 (breast cancer). The best results concerning the antiproliferative activity to kill cancer cells were obtained with the Au(III) dendron complexes bearing short alkyl chain length. Cell death pathway analysis reveals that the metaled dendrons could alter the cell cycle- and apoptosis-related protein status of cells, resulting in cell cycle S-phase arrest and apoptosis. In particular, Au(III)-complexes induced the caspase-dependent cellular lethality by promoting the translocation of Bax to the mitochondria and the release of Cyto C, whereas the Cu(II)-complexes are weak activators of caspase-3, in line with their moderate antiproliferative activity in cancer cells. Taken together, these studies showed that these first-in-class metaled phosphorus dendrons represent a novel class of anticancer nanodrugs, and their development will open new avenues to tackle cancers. Lastly, we prepared the amphiphilic phosphorus dendron 1-C12G1 bearing a long linear alkyl chain (C12H25), and bearing ten protonated pyrrolidine groups in the surface. 1-C12G1 forms nanomicelles which allow to encapsulate anticancer drug DOX and complex the miR-21 inhibitor. Especially, the encapsulation efficiency of DOX can reach up to 83.60%. Meanwhile, gel retardation assay showed that the miR-21i complexed by 1-C12G1@DOX were protected from degradation for up to 12 h and 24 h compared to the naked miR-21i.[...]
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Aloisi, Adriano. "Nanoparticles based on different generation adamantane dendrons : design, synthesis and self-assembly studies". Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAF062.
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L’adamantane est un hydrocarbure polycyclique, rigide et assez encombrant. En médecine, plusieurs dérivés à base d’adamantane ont été développés notamment comme agent antiviraux. Facilement fonctionnalisés, sa conformation 3D permet d’amoindrir les encombrements stériques entre les différents groupements fonctionnels. Nous avons décidé d’utiliser ses propriétés pour concevoir des structures plus complexes, à savoir, des dendrons et des foldamers. Les dendrons sont des polymères synthétiques possédant des propriétés intéressantes. De par leurs tailles, ils sont considérés comme des nanoparticules et possèdent un ciblage passif des cellules cancéreuses. De plus, facilement fonctionnalisés ils peuvent être utilisés comme molécule cargo dans la vectorisation de principes actifs. Outre la vectorisation, les dendrons permettent d’améliorer les propriétés physico-chimiques d’un médicament (absorption, distribution, métabolisme, élimination et toxicité). Nous avons alors choisi de concevoir des dendrons à base d’adamantane. Ces derniers ont la particularité de ne pas posséder d’espaceur entre les molécules d'adamantane se qui les rend hautement rigides. L’analyse par microscopie électronique à transmission de différents dendrons a permis d’étudier leurs morphologies selon leurs fonctionnalisations ainsi que l’effet du solvant, de la concentration et du support sur leurs auto-assemblages. Dans un second temps, nous avons conçu un acide aminé basé sur l’adamantane. Cet acide g-aminé a ensuite été incorporé dans des séquences peptidiques et les effets de l’adamantane sur la structure secondaire des peptides ont été étudiés par dichroïsme circulaireAdamantane is a polycyclic hydrocarbon, rigid and quite bulky. In medicine, several adamantane-based derivatives have been developed especially as antiviral agents. Easily functionalized, its 3D well-defined structure considerably decrease the sterical hindrance between its different functional groups. In this context, we decided to use adamantane to build more complex structures such as dendrons and foldamers. Dendrons are synthetic polymers with interesting properties. Because of their size, they are considered as nanoparticles and possess a passive cancer cell targeting. In addition,they are easily functionalized and can be use as vector of drugs. Indeed, the dendrons improve the physochemical properties of a drug (absorption, distribution, metabolism, elimination and toxicity). We decided to combine adamantane and dendrons to build adamantane-based dendrons. However, these dendrons have the particularity of not having spacer between the adamantane moieties, thus, they are highly rigid. Transmission electron microscopy analysis of the different functionalized dendrons allowed to study their self-assembly capacity and their morphology according to their functional groups,the solvent, the concentration and the support. In a second step, we designed an amino acid based on adamantane. This g-amino acid has been introduced in a peptide backbone using solid phase peptide synthesis. Then, the effects of adamantane onto peptide secondary structures have been studied by circular dichroism
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Fransen, Peter. "Synthesis and versatile applications of oligoethylene glycol dendrons using click chemistry". Doctoral thesis, Universitat de Barcelona, 2013. http://hdl.handle.net/10803/131404.
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Dendrimers are a class of globular highly branched macromolecules with precise architecture. They consist of a multivalent surface with functional group, a core unit where branching starts, and the interior is made of branching units and the void space in between the branched. Interesting properties of dendrimers are monodispersity, multivalency and a globular geometry.
Click chemistry is a ‘set of powerful, highly reliable, and selective reactions for the rapid synthesis of useful new compounds and combinatorial libraries’. The most commonly used click reaction is the copper-catalyzed azide-alkyne cycloaddition (CuAAC). Click chemistry is a powerful tool for the construction and functionalization of dendrimers.
The principle objective of the present thesis is the use of click chemistry for the synthesis of higher generation dendrons and exploring the possible use of these dendrons for biomedical applications.
The first generation dendrons which were synthesized in this work consist of two distinct parts: 1) a core unit derived from the acid diethylene triamine pentaacetic acid (DTPA); 2) monodisperse chains of oligoethylene glycol (OEG) of exact length which are coupled to the DTPA core unit by amide bond formation. The second and third generation dendrons were obtained in two steps: 1) conversion of the surface functional groups to azides; 2) coupling the azide building block unit to the azides of the core unit through CuAAC.
Apart from the synthesis of the dendrons using click chemistry, the present thesis also described some biomedical applications of the mentioned dendrons. The core unit derived from DTPA is orthogonally protected and this allows functionalizing the dendrons with distinct moieties. Furthermore, the DTPA derivative endows the dendrons the intrinsic capability to chelate metal ions. The chelation depends on the type of complexated metal ion and also on the functional group in the focal point of the dendron. The metals which can be chelated include gadolinium, terbium and indium, all of which are interesting for medical imaging purposes. Chelating gadolinium with dendrons increase the relaxivity induced by the gadolinium ion because the size of the dendrons slows down the rotation of the metal center. Also, the relaxivity is increased due to the hydrophilic character of the dendrons.
Combining the ability to chelate with the multivalency of the dendrons several multimodal platforms for medical imaging were constructed. The platforms were functionalized with targeting peptides and a fluorophore and the DTPA derived core unit carried an isotope of indium. Internalization assays demonstrated that the peptides were able to direct the platforms towards the targeted cells and other preliminary in vivo experiments indicated that the constructs accumulated in the tumors as shown in fluorescence and SPECT imaging.
Other dendrons were synthesized to serve as cross-linking agents of bio functionalization platforms. The cross-linking agents were composed of four azides and one bioactive moiety and are used to form hydrogels with the biopolymer hyaluronic acid. The biofunctionalization platforms were composed of four peptides and one azide for coupling the dendron. Using these platforms, peptides sequences could be introduced into the hydrogel and this works to augment the viability of the implanted cells.
Finally, an OEG-based dendron was used in combination with carbosilane dendrons to construct hybrid dendrons to bind DNA. The hybrid molecules displayed less cytotoxicity and were more effective delivering genetic material.
In conclusion, it has been demonstrated that click chemistry is a powerful tool for the synthesis and versatile applications of OEG-based dendrons.Los dendrímeros son una clase de macromoléculas que se caracterizan por tener una estructura altamente ramificada. Los dendrímeros contienen una superficie multivalente con los grupos funcionales, un núcleo donde empieza la ramificación eun interior constituido por los puntos de ramificación y los espacios vacíos entre las ramas. Las propiedades más interesantes de los dendrímeros incluyen su monodispersidad, multivalencia y geometría globular. La química click es un ¿grupo de reacciones que son poderosas, fiables y selectivas para la síntesis rápida de compuestos útiles y bibliotecas combinatorias¿. El mejor ejemplo de química click es la cicloadición catalizada por cobre entre azidas y alquinos (CuAAC). La química click es una herramienta poderosa para construir y funcionalizar dendrimeros. El objetivo principal de la presente tesis ha sido utilizar la química click para la síntesis de dendrones de generaciones elevadas y explorar la posibilidad de aplicar estos dendrones para aplicaciones biomédicas. Los dendrones de primera generación sintetizados en este trabajo consisten de dos partes distintas: 1) un núcleo derivado del ácido dietilentriaminopentaacético (DTPA); 2) unas ramas monodispersas de oligoetilenglicol (OEG) que se acoplan al núcleo de DTPA a través de la formación de un enlace amida. Los dendrones de generación 2 y 3 se pueden obtener mediante dos pasos: 1) la conversión de grupos funcionales en la superficie a azidas; 2) acoplando el building block dendron con un alquino a la azida a través de la CuAAC. Aparte de la síntesis de los dendrones utilizando la química click, la presente tesis también describe unas aplicaciones biomédicas de estos dendrones. El núcleo basado en DTPA está protegido de una manera ortogonal y esto permite funcionalizar los dendrones con grupos distintos. El derivado de DTPA también otorga a los dendrones una capacidad intrínseca de complejar iones de metales. La complejación depende del tipo de metal complejado y del grupo funcional en el punto pocal del derivado de DTPA. Los metales que se complejan incluyen gadolinio, terbio e indio, los cuales son interesantes para aplicaciones de imagen médica. Complejando gadolinio los dendrones aumentan la relaxividad causado por el ion de gadolinio porque el tamaño mayor de dendron ralentiza la rotación del metal. También la relaxividad se aumenta por el carácter hidrófilo de los dendrones. Combinando la capacidad de quelar con la multivalencia del dendron se construyeron distintas plataformas multimodales para la imagen médica. Las plataformas se funcionalizaron con péptidos diriguidores y un fluoroforo y el nucleo basado en DTPA llevaba un isotopo de indio. Ensayos de internalización mostraron que los péptidos eran capaces de dirigir las plataformas a las células dianas y unos experimentos preliminares in vivo indicaron que los constructos se acumularon en tumores lo cual se podía visualizar por fluorescencia y por SPECT. Se sintetizaron dendrones como agentes de cross-linking o plataformas de biofuncionalizacion. Los agentes de cross-linking llevan cuatro azidas y un grupo bioactivo y sirve para formar un hidrogel con el biopolímero acid hyaluronico. Las plataformas de biofuncionalizacion tienen cuatro péptidos y una azida para acoplar el dendron al biopolímero. Así se pueden introducir grupos peptídicos en el hidrogel y esto sirve para aumentar la viabilidad de las células implantadas Finalmente se utilizaron los dendron de OEG en conjunto con dendrones de carbosilano para preparar dendron híbridos para complejar ADN. Estos hibridos mostraron menos citotixicad y tenían una mayor capacidad de entregar material genético. En conclusión, se ha mostrado que la química click es una herramienta potente para la síntesis y aplicación diversa de dendrones basados en OEG.
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Grillaud, Maxime. "Design and synthesis of multifunctional adamantane-based dendrons for biological applications". Thesis, Strasbourg, 2014. http://www.theses.fr/2014STRAF021.
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Les polymères synthétiques tels que les dendrons ou les dendrimères possèdent des propriétés structurales intéressantes. Leur monodispersité et leur synthèse étape par étape permet de contrôler et de caractériser totalement leur structure. De plus, la multivalence offre aux vecteurs une meilleure affinité d’interactions entre plusieurs copies d’un ligand lié au dendron/dendrimère et le récepteur désiré en comparaison au ligand seul. L’adamantane est une molécule rigide et stable dont plusieurs dérivés ont été commercialisés pour des applications thérapeutiques, principalement comme agents antiviraux. De plus, il est possible de le fonctionnaliser sur 4 positions symétriques via des synthèses organiques. Sa conformation 3D permet d’amoindrir les encombrements stériques entre les groupements fonctionnels. Nous avons alors choisi de combiner les propriétés de l’adamantane et des dendrons afin de construire de nouveaux vecteurs synthétiques. Leurs synthèses s’effectuent avec de hauts rendements et chaque nouveau composé a été totalement caractérisé par les différentes techniques d’analyses chimiques et structurales. Les dendrons à base d’adamantane polycationiques non cytotoxiques ont révélé une forte pénétration cellulaire permettant de mieux comprendre les mécanismes d’internalisation des dendrons. Ils ont également été évalués pour la formation de complexes avec un plasmide d’ADN. Des modifications sur leurs structures ont amélioré leur capacité à interagir avec l’acide nucléique grâce à la modification du point focal. Enfin, un peptide thérapeutique aux propriétés protectrices dans le lupus érythémateux disséminé, P140, a été couplé à un dendron à base d’adamantane à 3 branches et nous avons analysé les effets biologiques du trimère en comparaison avec le monomèreDendrons (wedge-shaped dendrimer sections) have been investigated as ideal nanoscale carrier molecules for the delivery of bioactive materials into the cells. Molecular engineering of these hyperbranched, monodisperse, well-defined structures can be easily performed using simple organic synthesis. Multivalency constituted by the multiple surface groups at the periphery of a dendron promotes higher binding affinity for ligand/receptor interactions. Adamantane molecule is a rigid structure consisting of four cyclohexane rings fused in chair conformation. The well-defined 3D conformation, the hydrophobicity and the lipophilicity provide to adamantane-based compounds favorable properties for their transport through biological membranes. In this context, the first part of this work was focused on the design and the synthesis of a novel type of polycationic dendrons based on adamantane, which are able to penetrate into cells without triggering cytotoxic effects. The next study of this Thesis concerned the investigation of our polycationic adamantane-based dendrons for gene delivery. We evaluated the capacity of the dendrons to complex a plasmid DNA. Hydrophobic compounds (biotin and cholesterol) were covalently bound to the focal point of the dendrons via “click” chemistry and the effects of the dendron generation, the peripheral cationic groups, and the hydrophobic modifications on the formation and stability of the complexes were studied. Finally, the dendrons constituted of an adamantane core, a focal point and three arms, were synthetized starting from a multifunctional adamantane derivative. We have coupled P140, a therapeutic peptide with protective properties in systemic lupus erythematosus, to an adamantane-based dendron and we have analyzed the biological effects of the resulting trimer compared to the monomer
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Masheta, Dhafir. "Glutathione-decorated dendrons as potential drug carrier systems in Multiple Sclerosis". Thesis, University of Brighton, 2017. https://research.brighton.ac.uk/en/studentTheses/2209cd42-7ff3-4c05-85ec-e3f14ed4446e.
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Multiple sclerosis (MS) is a chronic progressive demyelinating disorder of the central nervous system. It is an autoimmune neurodegenerative disease associated with inflammation in the brain white matter mediated by autoreactive T-cells. MS is not curable and the treatment is only aimed at reducing the frequency, limiting the lasting effect of relapses, relief of symptoms, preventing disability arising from disease progression and promoting nerve repair. Glucocorticoid, typically methylprednisolone (MP) is given to reduce the duration of MS relapses. However, due to the presence of the blood-brain barrier (BBB) which impedes the effective delivery of MP to the brain, high doses of MP are given to the patients to reach the minimum therapeutic concentration. Consequently, such elevated doses of MP results in an increase in the adverse effects of the drug. To overcome MP limited permeability, it must be delivered using specialised strategies to avoid high doses administration. This study aims to improve MP cell membrane penetration employing dendrons as drug carriers to achieve higher loading capacities and utilising glutathione molecule as a ligand to be recognised by glutathione receptors in the brain. The aim was achieved by design and characterisation of dendron-drug conjugates, assessment of their cytotoxicity, validation of an in vitro b.End3 cells brain model, penetration studies through this model and biochemical investigation of the anti-inflammatory activity of the final molecule. The successful synthesis of the dendrimers, dendrimer-MP conjugates and attachment with glutathione were achieved using automated solid phase peptide synthesis and characterised by high performance liquid chromatograph, mass spectrometry, nuclear magnetic resonance and Fourier transform infra-red spectroscopy. The cytotoxicity of the drug loaded and unloaded was assessed using lactate dehydrogenase, MTT and calcein/ethidium cytotoxicity assays. Under the conditions used, the assembled drug conjugates’ toxicity levels were within the acceptable range. Transwell inserts were used to support mice immortalised brain endothelial cells, b.End3, to form an in vitro model of the BBB model. The model was validated by using transepithelial electrical resistance measurements, morphological examination, and permeability to paracellular marker (horseradish peroxidase). The data collected revealed that the b.End3 cell line is able to express several important barrier features of the in vivo BBB and can be used as in vitro BBB model for penetration studies. The cells exerted their maximum barrier functions at Day 7 of culturing. Fluorescent staining images confirmed the uptake of the synthesised molecules by b.End3 cells. Quantitative measurements based on high performance liquid chromatography of penetration through the b.End3 cultured cells-barrier indicated improvement in the permeability of MP conjugated to glutathione by almost 3.5 fold compared to free MP reaching 16.8% and 40.9% after 1 and 3 hours of sample introduction, respectively. Biochemical investigations revealed that MP in its attached form retained its anti-inflammatory activity based on the reduction in lactate dehydrogenase and inflammatory cytokines release levels from C6 glial cells treated with tumour necrotic factor- and showed greater antiinflammatory activity compared to unconjugated MP. It can be concluded that the ability of MP to cross an in vitro BBB model can be improved by using glutathione-dendronised carrier system and could provide a suitable base for other poorly penetrating medications intended for the treatment of other neurodegenerative diseases.
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Tang, Wen. "Bioactive Surface-Targeting Modular Peptide-Dendrons: Synthesis, Binding Affinity and Applicaiton". University of Akron / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=akron1406049913.
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Battigelli, Alessia. "Cationic carbon nanotubes for nucleic acids delivery". Thesis, Strasbourg, 2012. http://www.theses.fr/2012STRAF069.
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Les nanotubes de carbone (CNTs) sont une nouvelle forme allotropique du carbone, décrits pour la première fois à l’échelle atomique en 1991 par Iijima. Dans ce travail de thèse, les MWCNTs portant des charges cationiques ont été fonctionnalisés, avec pour objectif d’étudier leur aptitude à complexer des acides nucléiques pour obtenir un système de délivrance génétique. Initialement, nous avons fonctionnalisé les MWCNTs avec des dendrons portant à leur extrémité des groupes ammonium ou guanidinium et leur aptitude à complexer des acides nucléiques a été évaluée par électrophorèse en gel d’agarose. En outre, nous avons fonctionnalisé et caractérisé les MWCNTs avec un peptide ciblant les mitochondries et leur habilité à se localiser à l’intérieur de ces dernières a été étudié par différentes techniques microscopiques. Ensuite, nous avons doublementfonctionnalisé les CNTs avec un dendron de deuxième génération et avec le peptide de ciblage. La capacité de ce conjugué à complexer l’ADN a finalement été confirmée par électrophorèse en gel d’agaroseCarbon nanotubes (CNTs) are a new allotropic form of carbon described at the atomic level in 1991 by Iijima. During my thesis, carbon nanotubes bearing cationic moieties have been functionalized, in order to study their ability to complex the genetic material to obtain a gene delivery system. Initially we have functionalized MWCNTs with dendrons bearing at their termini ammonium or guanidinium groups. Their ability to complex the genetic material has been evaluated through agarose gelelectrophoresis. Moreover, we have functionalized and characterized MWCNTs with a targeting peptide for mitochondria and their ability to localize inside this organelle was studied by different microscopic techniques. Then, we have double-functionalized MWCNTs with a dendron of second generation and with the targeting peptide and the ability of this conjugate to complex DNA was confirmed by agarose gel electrophoresis
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Griffe, Laurent. "Dendrimères et dendrons phosphorés, de la chimie des matériaux à la biologie". Toulouse 3, 2004. http://www.theses.fr/2004TOU30258.
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Un dendrimère est une macromolécule constituée de monomères qui s’associent selon un processus arborescent autour d’un cœur central plurifonctionnel, via un procédé de synthèse itératif. Ce travail effectué en partenariat avec la société Rhodia® a démontré que la synthèse des dendrimères phosphorés ainsi que leurs architectures sont compatibles avec la chimie des phosphonates, des acides phosphoniques et de leurs dérivés salins. Nous décrirons la synthèse de ces nouveaux dendrimères, ainsi que de systèmes apparentés comme des dendrons, dans lesquels nous insèrerons ces fonctions, à divers niveaux architecturaux (le cœur, les branches ou la surface). Ces nouvelles macromolécules ont été greffées sur des surfaces métalliques d’Al et de Cu contrôlées par microscopie à force atomique. Une collaboration avec une équipe de biochimistes a permis de mettre à jour des perspectives thérapeutiques très prometteuses dans le domaine de l’immuno-stimulationDendrimer is a macromolecule constituted by monomers association via treelike process all around plurifunctional central core by way of iterative synthesis. This work has been performed with a financial support of Rhodia® industry. We demonstrated the compatibility of dendrimers containing phosphorus and their structures with phosphonates, phosphonic acids and salts derivatives chemistry. We will describe synthesis of these new dendrimers and dendron-like systems and the insertion of these several functions at different levels (core, branch, and surface) of these new macromolecules. Some of these new macromolecules have been grafted on metallic surface (Al or Cu) whose layers have been checked with atomic forces microscopy. We also collaborated with biologists’ team and demonstrated different bioactivity properties in immuno-stimulation fields
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Alami, Omar. "Oxyde de graphène fonctionnalisés par des dendrons et dendrimères pour des applications en oncologie". Thesis, Toulouse 3, 2022. http://www.theses.fr/2022TOU30086.
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Le graphène, une monocouche d'atomes de carbone densément tassée dans un réseau en nid d'abeille, a été isolé pour la première fois en 2004. Ces dernières années, la recherche sur le graphène et ses dérivés a suscité un intérêt considérable dans un large éventail d'activités de recherche grâce à ses propriétés intéressantes. La voie la plus facile et polyvalente pour obtenir des nanocomposites à base de graphène consiste à oxyder le graphite naturel pour obtenir l’oxyde de graphène (GO), un matériau ayant une surface riche en fonctions chimiques modifiables. Des nanocomposites à base d’oxyde de graphène ont été synthétisés pour des applications potentielles dans l'électronique, le stockage d'énergie, la catalyse et la sorption, le stockage, la séparation et la détection de gaz ainsi que dans le domaine biomédical. Les dendrimères sont des macromolécules particulièrement intéressantes pour un très grand nombre d'applications dans des domaines extrêmement variés. Cet intérêt réside essentiellement dans leurs propriétés de coopérativité et de multivalence, ainsi que dans leur très haute capacité d'encapsulation ou de fixation de petites molécules, et ceci dans un volume de taille nanométrique. Cette caractéristique structurale est la conséquence de leur architecture unique ramifiée contenant un cœur central et possédant de nombreuses fonctions périphériques. Les dendrimères sont donc des outils très intéressants pour la délivrance de médicaments et d'acides nucléiques. Dans ce travail nous allons développer des approches simples pour décorer la surface de l’oxyde de graphène avec des dendrons et dendrimères phosphorés pour des applications en oncologie. Dans un premier temps on va effectuer la synthèse des dendrimères phosphorés classiques, et des dendrons AB5, ensuite le greffage des différents monomères sur leur surface. En parallèle la préparation de l’oxyde de graphène (GO) ainsi que la modification de la surface de GO par différentes méthodes a été effectué, et finalement le greffage des différents dendrons sur la plateforme de l’oxyde de graphène a permis d'obtenir de nouveaux matériaux hybrides qui seront testés biologiquementGraphene, a monolayer of carbon atoms densely packed in a honeycomb lattice, was first isolated in 2004. In recent years, research on graphene and its derivatives has generated considerable interest in a wide range of research activities thanks to its interesting properties. The easiest and most versatile way to obtain graphene-based nanocomposites is to oxidize natural graphite to obtain graphene oxide (GO), a material with a surface rich in modifiable chemical functions. Graphene oxide nanocomposites have been synthesized for potential applications in electronics, energy storage, catalysis and sorption, gas storage, separation and detection as well as in the biomedical field. Dendrimers are particularly advantageous macromolecules for a very large number of applications in extremely varied fields. This interest resides essentially in their properties of cooperativity and multivalence, as well as in their very high capacity for encapsulation or fixing of small molecules, and this in a volume of nanometric size. This structural characteristic is the consequence of their unique branched architecture containing a central core and having many peripheral functions. Dendrimers are very interesting tools for the delivery of drugs and nucleic acids. In this work we will develop simple approaches to decorate the surface of graphene oxide with phosphorus dondron and dendrimers in order to create new hybrid materials with new properties. First, the synthesis of classical phosphorus dendrimers and of AB5 dendrons will be carried out, followed by the grafting of the different monomers on their surface. In parallel the preparation of graphene oxide (GO) as well as the modification of the GO surface with different methods will be carried out, and finally the grafting of the different dendrons on the platform of graphene oxide will afford new hybrid materials that will be biologically tested
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Pollock, Neal. "The synthesis, immobilisation and characterisation of poly(amidoamine) dendrons on plasma polymer thin films". Thesis, University of Sheffield, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.500151.
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Gonzaga, Rodrigo Vieira. "Pró-fármacos dendriméricos potencialmente cardiovasculares derivados de rosuvastatina e ácido acetilsalicílico: síntese dos respectivos dendrons". Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/9/9138/tde-16112017-172047/.
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As doenças cardiovasculares são as principais causas de morte no Brasil e no mundo e constituem problema de saúde médico-social, de grande impacto econômico. As alterações no perfil lipídico e hematológico são fundamentais na formação da aterosclerose, considerando que o LDL (do inglês Low-Density Lipoprotein) e a agregação plaquetária estão envolvidos na formação dos trombos e, consequentemente, em eventos vaso-oclusivos. Entre os fármacos utilizados, encontram-se as estatinas. A rosuvastatina, um dos fármacos utilizados, é inibidora da hidroximetilglutaril coenzima A (HMG CoA) redutase e possui melhor perfil farmacodinâmico entre as estatinas, com maior potência e seletividade. O ácido acetilsalicílico, anti-inflamatório não-esteroide com atividade antiplaquetária mais difundido na terapia, é utilizado, por esse efeito, em associação com estatinas. Fatores limitantes para o uso da rosuvastatina e o ácido acetilsalicílico são: a baixa permeabilidade da rosuvastatina cálcica, e consequente baixa biodisponibilidade (biodisponibilidade absoluta 20%), e tempo de meia-vida do ácido acetilsalicílico de 6-7 h, o que leva à necessidade de elevadas doses e maior frequência de administração de ambos os fármacos. Visto que a associação das estatinas e do ácido acetilsalicílico promove melhor eficácia na prevenção e tratamento de doenças cardiovasculares, o objetivo foi aumentar a solubilidade da estatina e, consequentemente, a sua biodisponibilidade, e a meia-vida do ácido acetilsalicílico, juntamente com a diminuição da toxicidade desse último.. Por outro lado, considerando-se a importância dos dendrímeros como transportadores de fármacos na latenciação, propôs-se o planejamento e a síntese de pró-fármacos dendriméricos, potencialmente cardiovasculares, derivados da associação de rosuvastatina e ácido acetilsalicílico, utilizando etilenoglicol e pentaeritritol como núcleos e ácido L(-)-málico, ácido 2,2-bis(hidroximetil)propiônico e etilenoglicol, como espaçantes.. Obtiveram-se dois pró-fármacos, que se constituem em dendrons como parte dos dendrímeros planejados. O primeiro foi sintetizado pelo método convergente em duplo estágio e faz parte do bloco da camada externa do dendrímero I e o segundo, pela abordagem convergente clássica, sendo este o dendron do dendrímero II. Parte limitante na obtenção desses dendrímeros, além das etapas de purificação, são as etapas de desproteção.Cardiovascular diseases have been the main causes of death in Brazil and in the world and are medical-social health problem with great economic impact. Alterations in the lipid hematological profiles are essentials in atherosclerosis, as LDL (Low-Density Lipoprotein) and the platelet aggregation are involved in the thrombus formation and, consequently, in occlusive vessel events. Among the drugs used to overcome those alterations are the statins. Rosuvastatin, one of the drugs used, is a hydroxymethylglutaryl coenzine A (HMG CoA) reductase inhibitor and it has the best pharmacodynamics profile among the statins, with higher potency and selectivity. Acetylsalicylic acid, a non-steroid anti-inflammatory agent with antiplatelet activity most disseminated in therapeutics, has been used in combination with statins due to this effect. Limited factors for the use of rosuvastatin and acetylsalycilic acid are the low permeability of the former, and consequently a low bioavailability (20% absolute bioavailability), and a 6 to 7 h half-life time of acetylsalycilic acid. Those factors lead to the need of high doses and higher frequency of administration of both drugs. Considering the combination of statins and acetylsalycilic acid promotes a better efficacy in either prevention or in the treatment of cardiovascular diseases, the objective of this work was to increase the rosuvastatin solubility and, consequently, its bioavailability, and the half-life time of acetylsalicylic acid, together with the decrease of its toxicity. On the other hand, considering the importance of dendrimers as drug carriers in prodrug approach, the design and synthesis of potentially cardiovascular dendrimer prodrugs derived from de combination of rosuvastatin and acetylsalicylic acid was proposed. With this goal, ethylene glycol and pentaerytritol were used as core and L(-)malic acid, 2,2-bis(hydroxymethyl)propionic acid and ethylene glycol were used as spacer groups. Two prodrug dendrons were obtained as part of the designed dendrimers. The first one was synthesized by two-step convergent method and it is part of the external layer block of dendrimer I. The second was obtained through classical convergent synthesis as the dendron of dendrimer II. The purification and deprotection steps showed to be the greatest obstacles for obtaining the proposed compounds.
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Kotta, Kishore Kumar. "Design, Synthesis, and Characterization of [1 → 3]; [1 → (2 + 1 Me)]; [1 → (2 + 1)] C-Branched Dendrons and Dendritic Architectures". Akron, OH : University of Akron, 2006. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=akron1137081672.
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Thesis (Ph. D.)--University of Akron, Dept. of Chemistry, 2006."May, 2006." Title from electronic dissertation title page (viewed 09/17/2006). Advisor, George R. Newkome; Committee members, Michael J. Taschner, David A. Modarelli, Chrys Wesdemiotis, Robert R. Mallik; Department Chair, Michael J. Taschner; Dean of the College, Ronald F. Levant; Dean of the Graduate School, George R. Newkome. Includes bibliographical references.
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Ramaswamy, Chandrasekaran. "Synthesis and characterisation of novel lysine based dendrons as non-viral vectors for gene delivery". Thesis, University College London (University of London), 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.413669.
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Issa, Rahaf. "Poly (ε-lysine) dendrons as effective modulators of virulence and biofilm formation in Pseudomonas aeruginosa". Thesis, University of Brighton, 2016. https://research.brighton.ac.uk/en/studentTheses/082dba11-68a1-44ec-b528-3d95b6fe9bfe.
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The opportunistic pathogen Pseudomonas aeruginosa is a significant contributor to multiple-drug resistant nosocomial and respiratory tract infections. In a vigorous search for alternative therapeutic approaches, innovative strategies that aim to modulate functions essential for infection have come to prominence. Natural and synthetic molecules capable of modulating virulence have been described. However, little is known regarding hyperbranched peptide-based macromolecules. The overall aim of this work was to determine the anti-virulence potential of poly (ε-lysine) dendrons against P. aeruginosa; their suitability as novel modulators of biofilm formation and virulence factor production, and their efficiency in an in vitro co-culture infection model. Using N-Fmoc solid-phase peptide synthesis, dendrons (consisting of an arginine root and branching points of lysine) were assembled onto a solid support to attain an asymmetrical hyperbranched structure. Dendrons with up to three branching generations (G) were successfully synthesised, as confirmed by high-performance liquid chromatography, mass spectrometry and Fourier transform infrared spectroscopy. The cationic charge of poly (ε- lysine) dendrons, exhibited as 16 terminal amine functionalities at G3, was predicted to enable dendron-bacteria interactions. In order to identify changes in cellular functions post-exposure to G3 dendrons, the metabolic activity of P. aeruginosa strain PAO1 was investigated. G3 dendrons induced a reduction in total RNA and protein synthesis, which caused a temporary (6h) growth arrest but did not affect the endpoint cell density. The anti-biofilm potential of G3 dendrons was assessed against PAO1 grown on three surfaces. G3 dendrons demonstrated a dosedependent effect against phenotypes associated with biofilm formation. As such, inhibition of swarming/swimming motility, reduction in surface coverage and microcolony formation, and attenuation of extracellular polymeric substance (EPS) matrix production reduced the bacterium’s biofilm forming capacity. The lack of EPS, which serves as a physical barrier when present, increased susceptibility to ciprofloxacin. Fluorescent labelling of G3 dendrons revealed their intracellular localisation and cell-penetrating capacity. Within 2h of incubation, G3 dendrons presented high uptake efficiency in PAO1 biofilms, and their accumulation at the inner poles of the cells was demonstrated using confocal microscopy. Free dendrons were rapidly released from the biofilm within 2-3 h. Using transcriptional and translational lacZ reporters, the regulation of virulence factors controlled by the las, rhl, and pqs networks of quorum sensing was investigated. G3 dendrons reduced the expression of two autoinducer synthases, lasI and rhlI, independent of changes to growth kinetics. Subsequently, the expression of genes that encode for elastase (lasB) and rhamnolipid (rhlA) production, and PQS (pqsA) signalling was downregulated. Complementation studies, using a lasI rhlI deficient mutant and exogenous autoinducers, demonstrated the ability of G3 dendrons to prevent biofilm formation, lascontrolled LasA protease and rhl-/pqs-controlled pyocyanin production. Using an optimised in vitro co-culture model of human bronchial epithelial (16HBE 14o-) cells and PAO1, the efficiency of G3 dendrons was evaluated. At a concentration non-toxic to 16HBE 14o- cells (0.8 mg/mL), G3 dendrons exhibited bacterial density-dependent protective properties. Specifically, a reduction in P. aeruginosa-induced cytotoxicity impaired the adherence and invasion of PAO1, and delayed the negative impact of PAO1 on the airway epithelial barrier function and integrity. In conclusion, this research highlights the anti-virulence effects of hyperbranched peptidebased macromolecules and constitutes a novel potential therapeutic. This may provide a non-antibiotic alternative for control and prevention of P. aeruginosa infections, and an effective approach to challenge the increasing resistance of bacteria to antibiotics.
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Koch, Susanne Julia. "Dendritic surface modification of photocatalytic nanoparticles for tumour therapy". Thesis, Bordeaux, 2017. http://www.theses.fr/2017BORD0687/document.
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L'apparition d’un développement cancérigène est souvent caractéristique des tumeurs de la région de la tête et du cou. En raison des altérations prémalignes et malignes fréquentes, il n'est souvent pas possible de supprimer complètement la tumeur par chirurgie.Il en résulte un risque élevé de récidive tumorale. Par conséquent, cette recherche de doctorat vise à développer des nanoparticules photocatalytiques (NPs) qui seront utilisées localement en complément de la thérapie tumorale traditionnelle. Ces NPs, une fois absorbées par les cellules tumorales induiront la mort des cellules photocatalytiques par activation de lumière UV. Des NPs de TiO2 ayant des propriétés photocatalytiques et une taille moyenne inférieure à 20 nm étaient donc synthétisées. La biocompatibilité des NPs, leur absorption dans les cellules et un ciblage tumoral efficace devraient être garantis par une modification de surface des particules avec des molécules organiques dendritiques permettant un contrôle précis de la charge de surface des particules ainsi que la possibilité de couplage avec des anticorps. Un autre objectif était la combinaison de propriétés thérapeutiques et diagnostiques dans le système de NPs par exemple réalisé par incorporation d'agent luminescent. Cette recherche était menée à l'Université de Bordeaux (synthèse des molécules organiques pour la fonctionnalisation des particules) en coopération avec l'Institut Fraunhofer de recherche en silicate ISC à Würzburg, Allemagne (synthèse des nanoparticules)The occurrence of field cancerization is characteristic for tumours of the head and neck region. Due to these widespread premalignant and malignant alterations, it is frequently not possible to entirely remove the tumour by surgery. This results in a high risk of tumour recurrence. Therefore, this PhD research aimed to develop photocatalytic nanoparticles (NPs) as completion of the traditional tumour therapy. These NPs are supposed to be incorporated by tumour cells and to induce photocatalytic cell death by UV light activation. TiO2 with convincing photocatalytic properties and an average size smaller than 20 nm should therefore be synthesized. NP biocompatibility, their uptake into cells and an efficient tumour targeting should be guaranteed by surface modification of the particles with dendritic organic molecules that allow a precise control of the surface charge of the particles as well as antibody coupling.A further objective was the combination of therapeutic and diagnostic properties within the NPsystem realized for example via introduction of a luminescent dye. This research was carried out at the University of Bordeaux (synthesis of organic molecules for particle functionalization) in cooperation with the Fraunhofer Institute for Silicate Research ISC in Würzburg, Germany (nanoparticle synthesis)
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McDaniel, Christopher George. "The Dendritic Effect on Enantioselectivity of Organocatalytic Reactions and the Effect of Local Compaction on a Titanium Mediated Allylation of Aldehydes". The Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1281293828.
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Pepiol, i. Martí Ariadna. "Síntesi i funcionalització d’o-carborans i metal·locarborans com a nuclis de dendrons i dendrímers. Aplicacions en medicina". Doctoral thesis, Universitat Autònoma de Barcelona, 2011. http://hdl.handle.net/10803/96765.
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La recerca que s’exposa en aquest treball de tesi es divideix en quatre parts: (1) el desenvolupament d'estratègies sintètiques per obtenir orto-carborans funcionalitzats sobre els vèrtexs de bor per tal d’aconseguir nanopartícules tipus arborol, (2) la síntesi i la caracterització d'un conjunt de clústers de bor simultàniament substituïts sobre els vèrtexs de carboni i els de bor, amb la finalitat de proporcionar precursors dendrítics versàtils que continguin grups funcionals terminals sobre els que serà possible assolir noves generacions, (3) síntesi d’orto-carborans Cc-iodats per avaluar la reactivitat en front de complexos fosfinidenoids de tungstè Li/Cl, (4) preparació de ciments ossis altament radioopacs per ser utilitzats en Vertebroplàstia mitjançant l'addició d’orto-carborans B-iodats.
El primer objectiu d'aquest treball va ser l'estudi de les diferents vies de síntesi per funcionalitzar orto-carborans B-iodats, per les seves potencials aplicacions en els camps de la medicina i dels biomaterials . Aleshores, mitjançant reaccions d’acoblament creuat de Kumada és possible per substituir els àtoms de iode per grups orgànics apropiats, de tal manera que, l’orto-carborà funcionalitzat que se n’obté es pot concebre com un nucli dendrític robust amb diverses ramificacions que pot oferir una plataforma única per a la construcció de molècules grans amb un control total sobre la posició de els substituents. El creixement de les estructures multibranca o arborols, on el nucli és una estructura d’orto-carborà, és ara possible gràcies a la síntesi de compostos que porten grups orgànics funcionals a la perifèria, com l’hidroxil, el clorur, el bromur, el tosil, l’àcid carboxílic o grups èster.
Un nou tipus de metal·lodendrímers polianiònics poli-(alquil-èter) han estat també preparats utilitzant la reacció d'obertura de l'anell del [3,3’-Co(8-OCH2CH2)2-1,2-C2B9H10)(1’,2’-C2B9H11)]. Aquest compost té un àtom d'oxigen unit a la posició del vèrtex B(8) amb una càrrega positiva i aquesta posició és susceptible a l'atac d’agents nucleòfils, com ara el grup alcoholat, que s’obté a partir de la desprotonació dels grups alcohol terminal (-OH) dels derivats di-, tetra -i hexa ramificats de l’o-carborà. El procés de degradació dels derivats de l’o-carborà closo B-iodats i B-alquilats amb agents bàsics genera els corresponents homòlegs nido i la subsegüent reacció de complexació amb cobalt dóna una substitució regioselectiva sobre els àtoms de bor del cobaltabis-dicarballur.
En aquest treball es presenta, per primera vegada, una sèrie de compostos ben definits i caracteritzats, derivats del cobaltabis-dicarballur, que proporcionen una seqüència artificial de descens del potencial entre grups donadors i receptors d'electrons, de compostos estructuralment molt similars. El creixement electroquímic del PPy dopat amb derivats poliiodats del cobaltabis-dicarballur mostra que el creixement dels polímers té poca dependència del nombre d’àtoms de iode però, en canvi, dependrà en gran mesura del seu E1/2(CoIII/CoII).
Finalment, els clústers de bor sintetitzats 4,5,7,8,9,10,11,12-I8-closo-1,2-C2B10H4 i 8,9,10,12-I4-closo-1,2-C2B10H8, han estat provats com a additius de contrast als raigs X en ciments ossis acrílics radioopacs per ser utilitzats en la tècnica de la Vertebroplàstia. S’ha realitzat una comparació de les principals propietats físiques i químiques que proporcionen els ciments ossis comercials que incorporen sulfat de bari com a agent de contrast i els ciments ossis que contenen derivats B-iodats de l’o-carborà. S’ha arribat a la conclusió que el segon tipus de ciment ossi dóna lloc a masses menys viscoses (més fàcilment injectables), presenta una excel·lent biocompatibilitat in vitro, així com radioopacitat suficient per ser utilitzat en Vertebroplàstia.The research explored in this Thesis work can be divided into four parts: (1) the development of synthetic strategies of multisubtituted ortho-carboranes on the boron vertexes in order to obtain arborol type functionalized unimolecular nanoparticles; (2) synthesis and characterization of a novel set of simultaneously Cc-disubstituted boron multisubtituted o-carborane derivatives, in order to afford new versatile dendritic precursors with terminal functional groups in which higher generations could be attained; (3) synthesis of Cc-iodinated o-carborane clusters to evaluate the reactivity towards Li/Cl phosphinidenoid tungsten complexes; (4) preparation of highly radiopaque bone cements for Vertebroplasty purpose by adding B-polyiodinated o-carboranes. The first aim of this work was the study of synthetic routes to functionalize B-iodinated ortho-carborane derivatives, which have possibilities in medicine and materials science. Functionalization reactions on 9,12-I2-closo-1,2-C2B10H10 and 8,9,10,12-I4-closo-1,2-C2B10H8 are accessible by the Kumada cross-coupling reaction, which allows the introduction of several organic moieties into the boron vertexes, such as allyl, phenyl or phenylethynyl unites. By substitution of iodine with the appropriate organic groups, the o-carborane cluster can be envisaged as a robust dendritic core for multiple and diverse types of ramifications, which may offer a unique platform for the construction of large molecules with full control over the position of the substituents. The growth of multibranched structures, or arborols, where the core is an ortho-carborane framework, is now open with the synthesis of compounds bearing functional organic moieties such as hydroxyl, chloride, bromide, tosyl, carboxylic acid, and ester groups on the periphery. Two or four arms may be densely appended to the cluster through four boron vertexes located at a compact area of the cluster, whilst the two C–H vertices occupying the two positions furthest away from them remain ready for further functionalization or complexation. A novel type of polyanionic poly-(alkyl-ether) metallodendrimers has also been prepared by using the ring opening reaction of the 8–dioxanate in [3,3’-Co(8-OCH2CH2)2-1,2-C2B9H10)(1’,2’-C2B9H11)]. This compound has an oxygen atom bonded to the B(8) vertex with a positive charge and this position is susceptible to the attack by nucleophiles, such as alcoholate functions obtained by deprotonation of the terminal alcohol groups (−OH) of di-, tetra- and hexa-branched o-carborane frameworks. The basic degradation process of closo B-iodinated and B-alkylated o-carboranes generates the corresponding nido counterparts and subsequent complexation reaction with cobalt affords well defined regioselective boron substituted cobaltabisdicarbollides. In this work we show a first case of an artificial large downhill sequence with well defined and characterized, and structurally very similar, individual electron donors and acceptors made from a common frame, the cobaltabisdicarbollide. Electrochemical growth of PPy doped with polyiodinated cobaltabisdicarbollide frameworks has been performed showing that any differences in the growth of PPy will depend little on the number of iodine substituents and largely on their E1/2(CoIII/CoII). Finally, previously synthesized boron iodinated o-carborane clusters, 4,5,7,8,9,10,11,12-I8-closo-1,2-C2B10H4 and 8,9,10,12-I4-closo-1,2-C2B10H8, have been tested as X-ray contrast additives in radiopaque acrylic bone cements for Vertebroplasty technique. Comparison of main physical and chemical properties between B-iodinated o-carborane containing cement and commercial BaSO4 cement has been established, concluding that the iodinated cement exhibited less viscous dough phase, excellent cell-compatibility in vitro, as well as sufficient radiopacity in a realistic experimental set-up.
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Kasëmi, Edis. "Efficient synthesis of homologous series of dendrons, dendrimers and dendronized polymers for supramolecular solution and bulk phase applications /". Zürich : ETH, 2007. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=17344.
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Kasemi, Edis. "Efficient synthesis of homologous series of dendrons, dendrimers and dendronized polymers for supramolecular solution and bulk phase applications". kostenfrei, 2007. http://e-collection.ethbib.ethz.ch/view/eth:29925.
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Preston, Adam J. "Structural and functional relationships in dendrimers Part 1: synthesis and study of liquid crystalline dendrimers as additives to dental composites. Part 2: effect of selective metal coordination on dendrimer structure /". Connect to this title online, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1104355003.
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Thesis (Ph. D.)--Ohio State University, 2005.Title from first page of PDF file. Document formatted into pages; contains xxvi, 533 p.; also includes graphics (some col.) Includes bibliographical references (p. 259-292).
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BINI, DAVIDE. "Synthesis of Glycoconjugates and their Analogs for the Study of Biological Systems". Doctoral thesis, Università degli Studi di Milano-Bicocca, 2016. http://hdl.handle.net/10281/103143.
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ABSTRACT
The project was focussed on the development of three main topics: a) trehalose mimics as trehalase inhibitors, b) synthesis of multivalent glycoconjugates and c) synthesis of glycosylated Pluronic block copolymers.
a) Trehalose mimics as trehalase inhibitors
Trehalase (α-glucoside-1-glucohydrolase, EC 3.2.1.28) is a specific glycosidase that catalyzes the hydrolysis of trehalose (α-D-glucopyranosyl-α-D-glucopyranoside) to the two constituent glucose units. This disaccharide is found in many organisms, but is absent in mammals. In insects, trehalose hydrolysis by trehalase is fundamental in various physiological processes. Given these premises, insect trehalases are attractive targets for the search of inhibitors as potential novel and selective insecticides. The aim of the project is the design, synthesis and in vitro and in vivo biological evaluation of some trehalose mimics (iminosugars or polyhydroxylated pyrrolizidine alkaloids) as selective insect trehalases inhibitors.
b) Synthesis of multivalent glycoconjugates
Recognition processes between glycans and their receptors are of paramount relevance in several biological phenomena, both in physiological and in pathological conditions. Moreover, most often these binding events occur in a multivalent and cooperative manner. In order to better understand these phenomena, dendrimers and dendrons have been developed to provide multivalent glycoconjugates. The aim of the project is the design and synthesis of new hetrobifunctional dendrons for carbohydrates multivalent presentation, and the study of synthetized glycoconjugates interactions with specific proteins.
c) Synthesis of glycosylated Pluronic block copolymers
Polymer-based nanotechnology became one of the most attractive and fast growing areas of pharmaceutical research. One promising example of such polymer nanomaterials is represented by a class of Pluronic block copolymers. In aqueous solutions, at concentrations above critical micelle concentration, these copolymers self-assemble into micelles. In application to anticancer chemotherapy, low molecular mass drugs encapsulation in micelles can diminish drug extravasation into normal tissues and provide for a passive drug targeting to tumors via the enhanced permeability and retention (EPR) effect. In order to gain also an active targeting effect on Pluronic micelles, I have been working on the design and synthesis of new glycosylated Pluronic block copolymers for antitumor drug delivery.
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Tomcik, Dennis John. "Part 1: Synthesis and Study of Helical Conformation in Chiral, Internally Hydrogen-Bonded Dendrons. Part 2: Synthesis and Study of Liquid Crystalline Dendrimers". The Ohio State University, 2003. http://rave.ohiolink.edu/etdc/view?acc_num=osu1048787071.
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Kantchev, Assen B. "Part 1, Oligosaccharide synthesis on a hyperbranched polymer as soluble support ; Part 2, Photoresponsive conformational equilibria of chiral, helically folded dendrons /". The Ohio State University, 2001. http://rave.ohiolink.edu/etdc/view?acc_num=osu1486572165275834.
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Moreno, Pierre. "Synthèse de dendrimères poly(aminoesters) biodégradables". Thesis, Aix-Marseille, 2013. http://www.theses.fr/2013AIXM4097.
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Les dendrimères sont une famille de macromolécules utilisées dans de nombreux domaines d’applications. Parmi ceux-ci, le domaine biomédical concentre une grande partie de l’intérêt de recherche. En effet, la structure tridimensionnelle parfaitement définie et monodispersée des dendrimères en font de parfaits candidats pour une application en médecine. Initialement utilisés en tant que mimes de protéines comme cela fût le cas lors du développement de la première famille de dendrimères, les poly(amidoamines) (PAMAM), de nombreuses études sur la capacité de transfection de ces molécules ont été réalisées, avec des résultats extrêmement encourageants. Afin d’améliorer l’efficacité et la biocompatibilité de ces vecteurs non viraux, nous avons orienté nos recherches sur le développement de nouveaux dendrimères poly(aminoesters) potentiellement biodégradables par hydrolyse enzymatique ou par variation de pH.Compte tenu des résultats précédemment obtenus au laboratoire, concernant la synthèse en solution de ces dendrimères, nous avons envisagé de les synthétiser en deux parties, à savoir un coeur central fonctionnalisé et des dendrons comportant la fonctionnalité appropriée. Notre choix s’est plus particulièrement porté sur la chimie « Click », en l’occurrence la cycloaddition 1,3-dipolaire de Huisgen entre un azoture et un alcyne catalysée par du cuivre. D’autre part, nous avons également envisagé de créer de nouveaux dendrons à l’aide de la chimie supportée. En effet, cette méthodologie de synthèse basée sur deux étapes répétitives d’addition de Michael et d’estérification, semble très prometteuse pour obtenir des dendrons de plus hautes générationsDendrimers are a special family of synthetic macromolecules with myriad applications, in particular biomedical implementation. The tridimensional, monodispersed and well defined structure of dendrimers give to them a unique position in medicine applications. Initially used as a mimic of proteins, poly(amidoamine) dendrimers (PAMAM) are also very efficient for nucleic acid delivery. With the aim to improve the biocompatibility and delivery efficiency of these non viral vectors, we designed and synthesized new poly(aminoester) dendrimers as potential biodegradable dendrimers sensitive to enzymatic hydrolysis or pH variations.On the basis of our previous results for the solution-phase synthesis of poly(aminoester) dendrimers, we decided to construct our dendrimers using a multi functionalized core and dendrons with complementary functions. These building units will be connected together at the end of the synthesis by a Huisgen dipolar cycloaddition through a copper-catalysed azide-alkyne cycloaddition (CuAAC) well known as « Click » reaction. In order to obtain higher generation dendrimers, we explore the supported chemistry using both soluble and solid supports. The solid-phase synthesis based on two iterative steps, Michael addition and esterification, seems to be very promising
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Rahma, Hakim. "Synthèse de nanofilms à greffons dendritiques pour l’immobilisation de biomolécules". Thesis, Bordeaux 1, 2012. http://www.theses.fr/2012BOR14593/document.
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La biofonctionnalisation de surfaces de silice est une étape cruciale dans de nombreux domaines de biotechnologie tels que la biodétection ou la bioséparation. Le contrôle de l’état de surface entre les supports solides des matériaux et les espèces biologiques permet d’améliorer leurs performances de reconnaissance. Dans ce travail, nous avons développés des organosilanes fonctionnels dendritiques de première et de seconde génération pour la modification chimique de surface. Ces organosilanes dendritiques de type RSiX3 (X= Cl ou OMe3 ou OEt3) ont été greffés de manière covalente sur des surfaces de silice ou des surfaces de nanoparticules superparamagnétiques de type core-shell (gamma-Fe2O3/SiO2). La qualité des greffages a été analysée par AFM et TEM. Ils ont également été caractérisés par infrarouge, angle de contact et zêtamétrie. Ces surfaces modifiées par des molécules dendritiques ont montré une capacité à immobiliser des molécules biologiques comme la protéine A ou des anticorps de lapinBiofunctionalization of silica surfaces represents a crucial step for many applications in biotechnology such as biosensing and bioseparation. Monitoring the surface modification of the materials supports can improve their performances for the recognition of biological species. In this work, we have developed functional dendritic organosilanes of first and second generation for chemical modification of surfaces. These dendritic organosilanes RSiX3 (X = Cl or OMe3 or OEt3) were covalently grafted on planar silica or on core-shell superparamagnetic nanoparticles surfaces (gamma-Fe2O3/SiO2). The grafted surfaces were analyzed by AFM and TEM. They were also characterized by Infrared, contact angle and zetametry. These modified surfaces by dendritic molecules have shown high ability to immobilize biological molecules such as protein A or rabbit antibodies
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Yu, Zhibo. "Amphiphilic cationic dendrons for the delivery of small interfering RNA in the treatment of rheumatoid arthritis Nanomedicines for the delivery of glucocorticoids and nucleic acids as potential alternatives in the treatment of rheumatoid arthritis A promising dual mode SPECT/CT imaging platform based on 99m Tc-labeled multifunctional dendrimer-entrapped gold nanoparticles". Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASQ015.
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Dans ce travail de thèse, nous avons sélectionné deux dendrons amphiphiles phosphorés (C17P10 et C11P10) pour leur potentiel en tant que système de délivrance de siRNA seul ou en combinaison avec la dexaméthasone (DXM) pour le traitement de la polyarthrite rhumatoïde. Le dendron C17P10 est capable de former des micelles et de complexer des siRNA, formant des dendriplexes qui ciblent TNF-α. Les dendriplexes de rapport N/P (azote/phosphore) de 5 ont été considérés comme un bon compromis en termes de taille, de la bonne affinité des siRNA et des quantités élevées de siRNA pouvant être véhiculés. Les dendriplexes entrainent une bonne inhibition du TNF-α in vitro dans des cellules Raw 264.7 activées par le lipopolysaccharide et un effet anti-inflammatoire significatif dans le modèle murin d‘arthrite rhumatoïde induite par le collagène. A l’issue des études in vitro et in vivo, l'effet des siRNA vectorisés par les siRNA s’est montré dose-dépendant et séquence-spécifique. Les dendriplexes ont pu induire une accumulation des siRNA dans les articulations inflammées par extravasation par voie vasculaire fuyante et séquestration à médiation cellulaire inflammatoire (ELVIS). Les dendrons amphiphiles (C11P10) portant une chaîne aliphatique C11 possèdent la capacité d’encapsuler la dexaméthasone et les siRNA par interaction électrostatique formant des dendriplexes nanostructurés chargés en DXM. Les dendriplexes chargés en DXM de rapport molaire dendron / DXM de 5 et de rapport N / P de 5 se sont révélés un bon compromis en terme de liaison des siRNA, des doses de DXM et de siRNA pouvant être injectées. Une activité anti-inflammatoire synergique de la dexaméthasone et des siRNA a été confirmée dans des cellules Raw 264.7 activées par le LPS. Nous pouvons conclure que les dendrons sont des vecteurs puissants et flexibles pour la délivrance de siRNA. Même s'il reste encore à étudier leur innocuité, ils semblent aussi efficaces que les lipides ou les polymères cationiques dans l'inhibition de TNF-αWe have screened out two amphiphilic phosphorus dendrons (C17P10 and C11P10) for their potential as delivery system for siRNA alone or in combination with dexamethasone (DXM) for the treatment of rheumatoid arthritis. C17P10 dendron can form micelles and bind TNF-α siRNA forming dendriplexes. Dendriplexes at the N/P (nitrogen/phosphorus) ratio of 5 were considered as a good compromise between size and good binding affinity for high siRNA concentration. They presented a good inhibition of TNF-α in vitro and significant anti-inflammatory effect in CIA mice model. The dose and sequence-dependent effect of siRNA in dendriplexes were demonstrated both in vitro and in vivo. Dendriplexes were able to induce siRNA accumulation in the inflamed paw by Extravasation through Leaky Vasculature and subsequent Inflammatory cell-mediated Sequestration (ELVIS). Amphiphilic dendrons (C11P10) bearing C11 aliphatic chain possess the capacity of loading dexamethasone and bind TNF-α siRNA through electrostatic interaction forming nanostructured DXM-loaded dendriplexes. DXM-loaded dendriplexes at the dendron/DXM molar ratio of 5 and the N/P ratio of 5 were a good compromise between good binding, high DXM dose, and high siRNA concentration. A synergistic anti-inflammatory activity between dexamethasone and siRNA was confirmed in LPS-activated Raw 264.7 cells. We believe that dendrons are potent and flexible carriers for siRNA delivery. Even if more need to be discovered about their innocuity, there are at least as much efficient as many cationic lipid or polymers in the inhibition of TNF-α
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Wen, Amy M. "Engineering Virus-Based Nanoparticles for Applications in Drug Delivery, Imaging, and Biotechnology". Case Western Reserve University School of Graduate Studies / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=case1452954511.
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Padié, Clément. "Dendrimères phosphorés : synthèse et applications". Toulouse 3, 2007. http://www.theses.fr/2007TOU30022.
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Les dendrimères sont des molécules nanoscopiques hyperbranchées dont la croissance itérative controlée autour d'un coeur plurifonctionnel permet l'obtention d'une structure sphérique parfaitement définie. La fonctionnalisation de surface de ces molécules leur permet d'acquérir des propriétés propres qui donne lieu à un grand nombre d'applications. Les travaux présentés sont articulés autour de cinq chapitres. Le premier chapitre consiste en une mise au point bibliographique concernant la synthèse de structures arborescentes et la pureté des espèces obtenues. Dans le deuxième chapitre, est développée la synthèse et l'étude spectroscopique de dendrimères dont la surface a été marquée sélectivement par le deutérium. Les études d'infrarouge ont permis d'accéder à des paramètres de forme et à des informations sur les structures obtenus pour les six générations de dendrimères synthétisés autour d'un cœur cyclotriphosphazène hexafonctionnel. Dans le troisième chapitre, La synthèse et les applications de dendrimères polycationiques solubles dans l'eau sont présentés. Dans une première partie, la fonctionnalisation de la surface du dendrimère par des chlorhydrate d'amine a permis d'envisager l'utilisation des entités obtenues dans le transport d'oligonucléotides fluorescents vers le noyau cellulaire. Dans une deuxième partie, la méthode de synthèse de dendrimères possédant un squelette hydrosoluble est discuté. Le quatrième chapitre traite de la synthèse de système multidendritique par association covalente de deux dendrons possédant des fonctions réactives à leur coeur. Les méthodes envisagées pour le couplage ont fait intervenir la réaction de Sonogashira, le couplage peptidique ou bien la formation d'une hydrazone. Le dernier chapitre est consacré àla fonctionnalisation des dendrimères phosphorés par des aza-bis(oxazolines) grâce àla réaction de cycloaddition 1,3-dipolaire (”Click chemistry”) entre un azoture et un alcyne. L'utilisation des molécules en tant que ligand pour la catalyse a été évaluée avec la réaction de résolution cinétique par benzoylation de mélanges d'énantiomères de l'hydrobenzoˆıne.
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Vestberg, Robert. "Dendron decorated chromophores for optical power limiting applications". Doctoral thesis, Stockholm, 2004. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-78.
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Schippling, Susanne. "Funktionelle Analyse von Dendrin zellbiologische Untersuchungen und Inaktivierung des Dendrin-Gens der Maus /". [S.l.] : [s.n.], 2000. http://deposit.ddb.de/cgi-bin/dokserv?idn=961678046.
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Moreno, Pierre. "Synthèse de dendrimères poly(aminoesters) biodégradables". Electronic Thesis or Diss., Aix-Marseille, 2013. http://www.theses.fr/2013AIXM4097.
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Les dendrimères sont une famille de macromolécules utilisées dans de nombreux domaines d’applications. Parmi ceux-ci, le domaine biomédical concentre une grande partie de l’intérêt de recherche. En effet, la structure tridimensionnelle parfaitement définie et monodispersée des dendrimères en font de parfaits candidats pour une application en médecine. Initialement utilisés en tant que mimes de protéines comme cela fût le cas lors du développement de la première famille de dendrimères, les poly(amidoamines) (PAMAM), de nombreuses études sur la capacité de transfection de ces molécules ont été réalisées, avec des résultats extrêmement encourageants. Afin d’améliorer l’efficacité et la biocompatibilité de ces vecteurs non viraux, nous avons orienté nos recherches sur le développement de nouveaux dendrimères poly(aminoesters) potentiellement biodégradables par hydrolyse enzymatique ou par variation de pH.Compte tenu des résultats précédemment obtenus au laboratoire, concernant la synthèse en solution de ces dendrimères, nous avons envisagé de les synthétiser en deux parties, à savoir un coeur central fonctionnalisé et des dendrons comportant la fonctionnalité appropriée. Notre choix s’est plus particulièrement porté sur la chimie « Click », en l’occurrence la cycloaddition 1,3-dipolaire de Huisgen entre un azoture et un alcyne catalysée par du cuivre. D’autre part, nous avons également envisagé de créer de nouveaux dendrons à l’aide de la chimie supportée. En effet, cette méthodologie de synthèse basée sur deux étapes répétitives d’addition de Michael et d’estérification, semble très prometteuse pour obtenir des dendrons de plus hautes générationsDendrimers are a special family of synthetic macromolecules with myriad applications, in particular biomedical implementation. The tridimensional, monodispersed and well defined structure of dendrimers give to them a unique position in medicine applications. Initially used as a mimic of proteins, poly(amidoamine) dendrimers (PAMAM) are also very efficient for nucleic acid delivery. With the aim to improve the biocompatibility and delivery efficiency of these non viral vectors, we designed and synthesized new poly(aminoester) dendrimers as potential biodegradable dendrimers sensitive to enzymatic hydrolysis or pH variations.On the basis of our previous results for the solution-phase synthesis of poly(aminoester) dendrimers, we decided to construct our dendrimers using a multi functionalized core and dendrons with complementary functions. These building units will be connected together at the end of the synthesis by a Huisgen dipolar cycloaddition through a copper-catalysed azide-alkyne cycloaddition (CuAAC) well known as « Click » reaction. In order to obtain higher generation dendrimers, we explore the supported chemistry using both soluble and solid supports. The solid-phase synthesis based on two iterative steps, Michael addition and esterification, seems to be very promising
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Najjar, Iris [Verfasser]. "Polysulfatierte Dendrone als Transportvehikel für Enzyme in der Tumortherapie / Iris Najjar". Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2018. http://d-nb.info/1160514992/34.
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Walter, Aurélie. "Élaboration de nano-objets magnétiques dendronisés à vocation théranostic". Thesis, Strasbourg, 2014. http://www.theses.fr/2014STRAE020/document.
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Cette thèse présente la conception de nano-objets magnétiques dendronisés permettant à la fois le diagnostic par imagerie par IRM et la thérapie par hyperthermie magnétique (HM). La validation in vitro et in vivo des propriétés de ces nano-objets et la démonstration de leur efficacité pour le ciblage spécifique de tumeurs sont rapportées. Un état de l’art sur la synthèse des NPs d’oxydes métalliques, leur fonctionnalisation ainsi que leurs propriétés en IRM et en HM est présenté. L’influence de la méthode de fonctionnalisation de NPs d’oxyde de fer puis l’influence de l’architecture de la molécule greffée sur la stabilité colloïdale et la relaxivité ont été étudiées. Des NPs de différentes tailles, morphologies et composition ont ensuite été synthétisées et fonctionnalisées par une molécule dendron et leurs les propriétés en IRM et en HM ont été étudiées. Le ciblage spécifique de la mélanine au sein de mélanome a été montréThis thesis presents the design of dendronized magnetic nano- objects for both diagnostic imaging by MRI and magnetic hyperthermia therapy (HM). In vitro and in vivo validation of these nano-objects properties and the demonstrattion of their effectiveness for specific targeting of tumors are reported. A state of the art on the synthesis of metal oxide NPs, their functionalization and their properties in MRI and HM is presented. The influence of the NPs iron oxide functionalization method and the influence of the molecule architecture on the colloidal stability and relaxivity were studied. NPs of different sizes, morphologies and composition were then synthesized and functionalized with a dendron molecule and the MRI and HM properties were investigated. The specific targeting of melanin in melanoma was demonstrated
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Saunders, Kate Marie. "Silurian dendroid graptolites : taxonomy, palaeoecology and biostratigraphy". Thesis, University of Portsmouth, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343388.
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Battigelli, Alessia. "Cationic Carbon Nanotubes for Nucleic Acids Delivery". Doctoral thesis, Università degli studi di Trieste, 2012. http://hdl.handle.net/10077/7416.
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2010/2011Carbon nanotubes (CNTs) are a new form of carbon discovered in the ’50/’60, but described at the atomic level only in 1991 by Iijima. CNTs are constituted by one or more rolled up graphene sheets and they can be classified in single-walled carbon nanotubes (SWCNTs) or multi-walled carbon nanotubes (MWCNTs). The peculiar properties of CNTs, characterized by their physical, chemical and mechanical properties, by their thermic conductivity and their large aspect ratio, rendered this material a promising candidate in several research fields, such as material science and nanotechnology. Recently, it has been discovered that CNTs have the ability to be uptaken by different types of human cells with a typical non-energy dependent mechanism called “nanoneedle”. This new property rendered CNTs a promising candidate as a vector for drugs. In this context, during my thesis I focused on the functionalization of carbon nanotubes bearing cationic moieties, in order to study their ability to complex the genetic material for a potential gene therapy. In the first part of the thesis MWCNTs were functionalized with different cationic dendrons and their capability to interact with plasmid DNA and siRNA (small interfering RNA) was evaluated. In the second part of the thesis, I focused on the functionalization of MWCNTs with a targeting peptide for mitochondria and the consequent possibility to use these conjugates as gene delivery system in mitochondrial diseases. Initially, a library of compounds with a ramified structure was synthesized. Dendrons of zero, first and second generation were obtained, bearing at their termini ammonium or guanidinium moieties, for the interaction with the genetic material. Two groups of dendrons were synthesized with two different functions at their core: i) an amine or ii) an azide. This was realized in order to have the possibility to link the dendrons to CNTs, exploiting two covalent approaches, the amidation reaction or the “click” reaction, respectively. In parallel a non-covalent approach was also investigated, coupling by “click” reaction a dendron of first generation to a pyrene bearing an acetylenic group. The resulting molecule was then adsorbed on the surface of MWCNTs, exploiting the known ability of pyrene to interact with nanotubes through “π-π stacking”. The conjugates obtained in this way were characterized by complementary techniques, such as thermogravimetric analysis, Kaiser test and transmission electron microscopy, allowing in this way to assess the degree of functionalization of CNTs and to observe their morphology. The ability of these conjugates to complex plasmid DNA and siRNA was studied through agarose gel electrophoresis using different charge ratios of genetic material and cationic CNTs. Preliminary cellular studies on guanidinium derivatives, to evaluate the effective ability of the conjugates to be internalized into human cancer cells (A549 cells), were performed in collaboration with Prof. K. Kostarelos and Dr. K. T. Al-Jamal in London. Further studies are currently under development to determine the aptitude of the derivatives to carry and deliver siRNA inside cells. The efficient gene silencing and the eventual cytotoxic effects of MWCNTs conjugates will be also studied into human cells. In the second part of the thesis, we focused on the development of a new gene delivery system able to direct the genetic material inside mitochondria, for a possible treatment of genetic diseases caused by mutation in the mitochondrial genome. To this purpose MWCNTs were functionalized with a targeting peptide (mitochondrial target sequence peptide, MTS) able to direct CNTs into mitochondria. The effective internalization of the material inside macrophages (RAW 264.7) and human cancer cells (HeLa cells) and their subcellular localization were studied through different microscopic techniques. Using confocal microscopy it was possible to observe a co-localization of CNTs and mitochondria, then confirmed also by TEM images. This latter technique permitted also to evaluate the possible mechanism used to internalize CNTs: i) “nanoneedle” mechanism and ii) phagocytosis (for macrophages) or endocytosis (for HeLa cells). In order to shed further light on the ability of CNTs to interact with mitochondria, nanotubes were double functionalized with the targeting peptide MTS and with a mitochondrial toxic peptide, called sVpr. The toxic effects of this material, in comparison with CNTs functionalized just with the toxic peptide, were studied on isolated mitochondria. The internalization of different conjugates into isolated mitochondria was then analysed by TEM. This work has been performed in collaboration with Prof. P. Bernardi (Università degli Studi di Padova). In order to obtain a system able to complex DNA, a double functionalization of CNTs was developed, coupling to the carbon material the targeting peptide MTS and a dendron, for the complexation of genetic material. The ability of this conjugate to interact with plasmid DNA was then verified through agarose gel electrophoresis, revealing its potentiality as efficient gene delivery system. In conclusion, in this work MWCNTs were functionalized with cationic dendrons, showing their ability to interact with the genetic material. Moreover when incubated into cells, the aptitude of MWCNTs, functionalized with a targeting peptide, to be directed in the proximity of mitochondria and to localize in their interior was demonstrated using different microscopic techniques. These results show the potentiality of this material in the field of nanomedicine, resulting a promising vector in gene therapy.
XXIV Ciclo
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Ribeiro, Suzie Jesus. "A study of DNA/Dendron nanoparticles for genetic immunisation against anthrax". Thesis, University College London (University of London), 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.439784.
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Bryden, Francesca. "Synthesis of water-soluble porphyrin-dendron conjugates for targeted photodynamic therapy". Thesis, University of Hull, 2013. http://hydra.hull.ac.uk/resources/hull:17231.
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The targeting of photosensitisers with tumour-associated biomolecules is widely used for improved photosensitiser tumour localisation during photodynamic therapy, allowing fewer side effects in comparison to conventional cancer treatments. In particular, conjugation to antibody fragments allows exploitation of their high affinity towards tumour-associated antigens; however current methods of conjugating porphyrins to antibody fragments represent a compromise between high binding ratios and good stoichiometric and site-specific control. The work presented herein addresses this problem through the synthesis of porphyrin-dendron conjugates and their attachment at the interchain disulfide bridge of antibody fragments, allowing improved binding ratios while maintaining good structural control. Synthesis of a range of click-functionalised porphyrins and dendrons bearing complimentary peripheral functionalities was carried out, followed by click conjugation of these structures under microwave irradiation to produce a range of lipophilic and hydrophilic porphyrin-dendron conjugates with between two and four peripheral porphyrins. Photophysical evaluation demonstrated retention of UV-vis and fluorescent character of porphyrins after conjugation, with some quenching of UV-vis absorption observed due to the close proximity of the porphyrins. Singlet oxygen quantum yields showed some quenching in all conjugates, with more sterically hindered systems showing the greatest reduction in SOQY in comparison to control porphyrins. Conjugation of porphyrins to a HER2-targeted Herceptin™ Fab fragment was carried out through pre-conjugation of an alkyne-dibromomaleimide heterobifunctional linker to the Fab fragment, with two examples of cationic porphyrins conjugated via a click chemistry strategy to yield conjugates with precise 1:1 stoichiometry. Preliminary cytotoxicity studies of the targeted photosensitisers showed that both conjugates exhibited limited dark toxicity, and excellent cell killing in the HER2+ BT-474 cell line. Successful focal-point deprotection and azide functionalisation was carried out on a single porphyrin-dendron conjugate, with a successful model click reaction to an alkyne-functionalised sugar displaying the possibility of bioconjugation of porphyrindendron conjugates via a click methodology.
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Aniejurengho, Orode Uche Venitia. "Dendron-based synthetic bacteriophages for the treatment of Proteus mirabilis infections". Thesis, University of Brighton, 2016. https://research.brighton.ac.uk/en/studentTheses/0aa0ac9f-6b96-416b-9556-bcbf9a540290.
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In the last two decades a surge in antibiotic resistance has limited antibiotic effectiveness increasing the risk of uncontrolled epidemics especially for biofilm-related infections. The National Institute of Health reports that 80 % of human infections are biofilm related. The Proteus mirabilis bacteria were focused on in this study as they are significant biofilm formers in chronic infections such as biofilm-related urinary tract infections for which there are currently no completely effective treatment strategies. As biofilms can increase antibiotic resistance by up to 1000-fold, there is an urgent need for the development of novel antimicrobials. Thus, bacteriophages which are viruses that target and kill bacteria have been proposed as suitable alternatives, but factors like storage stability and re-isolation pose limitations. Towards investigating the development of new antimicrobial strategies, the aims of this thesis were to assess: (i) the therapeutic potential of bacteriophages against Proteus mirabilis biofilms and (ii) the development of a novel antimicrobial strategy based on a synthetic biology approach for improvement of bacteriophage-based biofilm control. The work presented in this thesis led to or may lead to four areas of development, which have the potential to contribute to fields of biofilm research, bioengineering and materials science. Firstly, novel bacteriophages against clinical strains of Proteus mirabilis were isolated with physicochemical and genomic characterisation. Unlike other studies, the effect of temperature was included in the selection of favourable bacteriophages for anti-biofilm use. Secondly, towards improving bacteriophage-based treatment, dendrimeric nanoparticles known as dendron were posed as alternatives, these were synthesised and characterised, and demonstrated improved biofilm reduction and eradication by 35 % and 100 % respectively compared with the most effective bacteriophage. Thirdly, this study developed insight into the dendron’s mechanism of action, which was previously unreported, and was proposed to be through disruption of Proteus mirabilis DNA systems. Fourthly, in a unique approach, the dendron was bioengineered with bacteriophage DNA using electrostatic interactions. The results suggested that the dendron has potential to be used as a carrier for bacteriophage DNA, and presents the first attempt in published literature at combining the anti-biofilm properties of bacteriophages and dendrons towards futuristic development of synthetic bacteriophages. The results also provide a promising antimicrobial strategy for use of dendrons as therapeutic agents, alone or in combination with antibiotics and bacteriophages for treatment of biofilm-related infections.
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Evans, Rowan. "Reproduction of the unitary, larviparous ascidian Dendroda grossularia". Thesis, University of Liverpool, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.260360.
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Tie, Chenyang. "Conformation and Assembly Research on Dendron Derivatives: Azobenzene Oligomers and Dendritic Peptides". The Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1282077432.
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Perugini, Valeria. "Poly-ɛ-lysine dendron aptamers as regulators of angiogenesis in tissue regeneration". Thesis, University of Brighton, 2013. https://research.brighton.ac.uk/en/studentTheses/937e14a0-921a-4004-af1d-bbd97f6cd425.
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The successful regeneration of damaged or injured tissues is strictly dependent upon the ability to control angiogenesis. The formation of new blood vessels from pre-existing ones is mainly regulated by the vascular endothelial growth factor (VEGF), a mitogen specific for endothelial cells. A number of therapeutic approaches are being pursued to control this process in pathological conditions, including the use of synthetic peptides which have shown their capacity to either promote or inhibit angiogenesis. However, their lack of stability and short half-lives have strictly limited their clinical applications. To address these limitations, here, both anti- and pro- angiogenic peptide sequences (WHLPFKC and YIGSR) were synthesised at the uppermost branching generation of poly-ɛ-lysine dendrons.
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Schneider, Jérémy. "Synthèse d'une diversité de glycoclusters : effet multivalent sur l'inhibition des glycosidases". Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAF005.
Texto completo da fonteResumo:
Les premiers iminosucres multivalents rapportés dans la littérature datent de 1999. Depuis, c’est plus d’une centaine de clusters de ce type qui ont été synthétisés et décrits une quarantaine de publications. L’obtention d’un premier effet multivalent fort sur une glycosidase, en 2010, a initié de nouveaux travaux visant à étudier et à comprendre son mécanisme et ses limites. Dans cette optique le présent travail de thèse a exploité plusieurs approches. La première partie décrit la synthèse de dendrons "cliquables" permettant de multiplier par trois ou par neuf la valence initiale des plateformes utilisées. La deuxième est une étude de la synthèse d’espaceurs rigides. La troisième est la préparation de plateformes modulables, des neo-cyclodextrines, pour obtenir un contrôle plus fin de la topologie des clusters. L’association de dendrons "cliquables" et de plateformes cyclopeptoïdes de dimensions contrôlées a abouti à un résultat sans précèdent en termes d’effet multivalent. Ainsi, le cluster 36-valent à ligands DNJ est un inhibiteur 170 000 fois plus fort que l’analogue monovalent correspondant sur l’alpha-mannosidase des pois sabre blanc (Jack Bean)The first multivalent iminosugars were published in 1999. From this date, it’s more than a hundred of clusters that were synthesized and presented in about forty publications. In 2010, the first strong multivalent effect in glycosidase inhibition was obtained and prompted further studies of its mechanism and its limits. To reach these goals, this PhD work has developed different strategies. The first was to synthesize "clickable" dendrons which can lead to a multiplication of the initial valency of our scaffolds by three or by nine. The second approach was a study to obtain rigid linkers. The third one was the preparation of modular scaffolds, neo-cyclodextrins, in order to finely tune the topology of the resulting clusters. The combination of our "clickable" dendrons with cyclopeptoid scaffolds gave an unprecedented multivalent effect on glycosidase inhibition. The 36-valent DNJ-based cluster is indeed a 170 000-fold more potent inhibitor than the corresponding monovalent control for Jack Bean alpha-mannosidase
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Amorin, Rosario Daniel. "Synthèse et recyclage de catalyseurs métallodendritiques par leur greffage sur des nanoparticules magnétiques". Thesis, Bordeaux 1, 2009. http://www.theses.fr/2009BOR13953/document.
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La récupération et le recyclage des catalyseurs représentent un véritable challenge économique, sanitaire et environnemental. Depuis quelques années, l’utilisation des nanoparticules magnétiques comme support de catalyseurs a émergé comme une voie alternative pour leur recyclage. En effet, les catalyseurs supportés sur des nanoparticules magnétiques peuvent être facilement isolés et recyclés par décantation magnétique avec un simple aimant. Dans ce travail, nous décrivons la synthèse de métallodendrons porteurs de site catalytiques diphosphinopalladium et leur greffage sur des nanoparticules magnétiques cœur-écorce. L’intérêt majeur de ce travail a été de montrer la grande efficacité du recyclage des catalyseurs notamment en milieu aqueux. L’utilisation judicieuse des structures dendritiques a permis d’augmenter la fonctionnalisation de la surface des MNPs. Ceci nous a permis de préparer des catalyseurs supportés très performants dans des réactions de couplage de Suzuki et de SonogashiraThe recovery and recycling of catalysts represent a real challenge for economic, health and environmental reasons. Since few years, the use of magnetic nanoparticles as catalysts supports has emerged as an alternative for their recovery. Indeed, magnetic nanoparticles-supported catalysts could be easily isolated and recycled from the reaction medium by magnetization with a simple magnet. In this work, we report the synthesis of metallodendrons bearing pallado phosphine catalysts and their grafting onto core-shell magnetic nanoparticles. The main interest of this work was to demonstrate the efficiency of the recycling especially in aqueous media. Judicious use of dendritic structures has increased the surface functionalization of nanoparticles. Therefore, it was possible to prepare highly performant catalysts for Suzuki and Sonogashira cross-coupling reactions