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Novel Therapeutic Delivery via Cell-Nanoparticle HybridizationCooper, Remy C 01 January 2017 (has links)
The immobilization of surface-modified polyamidoamine (PAMAM) dendrimers on the cell surface introduces a novel approach for efficient and specific cellular uptake of therapeutic-carrying nanoparticles. This cell surface-nanoparticle hybridization event takes place via bioorthogonal copper-free click chemistry between a dibenzocyclooctyne (DBCO) group on the dendrimer surface and azide-capped glycans expressed on the cell membrane through metabolic incorporation of azido sugars. This particular cell-nanoparticle hybridization method can be exploited to deliver a variety of therapeutic, genetic or fluorescent payloads directly into cells. Here, this method was employed to deliver plasmid DNA, siRNA and the hydrophobic anticancer drug Camptothecin (CPT) to enhance transfection and therapeutic efficacy. Native, acetylated, and PEGylated generation 4 (G4) PAMAM dendrimers were conjugated with DBCO. When introduced to azide expressing NIH3T3 fibroblasts and HN12 cancer cells, successful surface hybridization was achieved. The physiochemical properties of PAMAM dendrimers allowed for successful hydrophobic drug encapsulation and electrostatic nucleic acid condensation.
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Stabilization of Submicron Metal Oxide Particles in Aqueous MediaGibson, Fredrick W. Jr. 30 July 1998 (has links)
An investigation into the parameters that define a good anchor block for a copolymer steric stabilizer was performed. The study focused on the effects of different functional groups on the adsorption properties of polymers. In addition, the effect of chain architecture as well as the impact of a hydrophobic end-group on polymer adsorption properties was determined. To complement the adsorption studies, a streaming potential instrument was built for use in measuring the adsorbed layer thickness of nonionic polymers on SiO₂. The research concluded with an examination of the effect of thermally induced insolubility on adsorption of a hydrogen-bonding polymer.
Functional group effects were studied by measuring the adsorption isotherms of poly(2-ethyl-2-oxazoline), PEOX, poly(ethylene oxide), PEO, poly(vinyl alcohol), PVOH, and poly(ethylene imine), PEI, which was modified such that a 1,3-butanediol substituent replaced its imine hydrogens, on SiO₂, TiO₂, and Al₂O₃. PEOX and PEO, relatively basic polymers compared to PVOH were observed to adsorb only on the most acidic metal oxide, SiO₂. PVOH, however, was observed to adsorb on all three metal oxides, but to a lesser degree on SiO2 as compared to the more basic PEOX and PEO. These initial results were indicative of hydrogen-bonding mechanisms, a form of acid-base interaction.
The most significant observation in the adsorption studies was that the linear hydroxyl modified PEI materials and their dendritic analogs adsorb on the metal oxides both above and below the i.e.p. This indicates that both electrostatic and hydogen-bonding mechanisms are driving the adsorption. The dendritic polymers, particularly a 4th generation dendrimer based on diaminopropane with a molecular weight of 16,640 g/mol adsorbed at a higher level when compared to the 41.3K g/mol PVOH and 30K g/mol PEOX. In addition to the dual adsorption mechanism, it was determined that the dendritic architecture appears to facilitate adsorption, as does the presence of the hydrophobic endgroup. The level of adsorption for all of the hydroxyl containing linear PEI and dendritic materials on the three metal oxides was high enough for them to be considered as anchor blocks in a copolymer steric stabilizer.
The streaming potential instrument used to measure the adsorbed layer thickness on SiO₂. Adsorbed layer thickness of PEOX Mw = 10K and 30K g/mol were measured at approximately 1nm and 4.4 nm, respectively. In the case of the PEOX Mw = 30K g/mol homopolymer, the measured layer thickness was higher than that for a 23K g/mol PEO homopolymer. The degree of polymerization of the PEO is approximately 525, while for the PEOX it was only 300. This result was not expected.
Finally, adsorption of PEOX was studied at the cloud point to determine whether insolubility could promote adsorption, while hydrogen-bonding, the room temperature driving force for adsorption, would decrease. Adsorption isotherm measurements were performed at 72 °C, and 75 °C, as the cloud point of the 30K PEOX was determined to be 73 °C. It was apparent that the adsorption decreased as temperature increased, indicating that without hydrogen bonding, thermally induced insolubility does not drive adsorption. / Ph. D.
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Study of Nanoparticle/Polymer Composites: I) Microstructures and Nonlinear Optical Solutions Based on Single-Walled Carbon Nanotubes and Polymers and II) Optical Properties of Quantum Dot/Polymer CompositesWoelfle, Caroline 17 May 2006 (has links)
The overall research theme of this dissertation was the study of nanoparticle/polymer composites. Two types of nanoparticles were utilized: Single-Walled Carbon Nanotubes and quantum dots. Chapter 1 of this thesis comprises an extensive literature review on Carbon Nanotubes, which presents theoretical aspects relevant to the structure and properties of CNTs, methods of purifying and solubilizing CNTs in aqueous and organic solvents and selected applications. This literature review is followed by the study and comparison of the optical limiting performances of different Single-Walled Carbon Nanotubes/conjugated polymer dispersions (Chapter 2). The results obtained are discussed in terms of dispersion of the SWNTs in the polymer solutions and resulting SWNT bundle diameters. Chapter 3 presents the spontaneous assembly of dendrimer patterns induced by SWNTs. Finally, chapter 4 presents a new method for fabricating quantum dot/polymer composites, which uses the extraction of positively charged quantum dot into a hydrophobic liquid. The resulting solution is used as a compatible polymerization medium for poly(methylmethacrylate ) networks enabling the formation of transparent and fluorescent composites. / Ph. D.
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Underpotential deposition as a synthetic and characterization tool for core@shell dendrimer-encapsulated nanoparticlesCarino, Emily V. 10 January 2013 (has links)
The synthesis and characterization of Pt core/ Cu shell (Pt@Cu) dendrimer-encapsulated nanoparticles (DENs) having full and partial Cu shells deposited via electrochemical underpotential deposition (UPD) is described. Pt DENs containing averages of 55, 147, and 225 Pt atoms immobilized on glassy carbon electrodes served as the substrate for the UPD of a Cu monolayer. This results in formation of Pt@Cu DENs. Evidence for this conclusion is based on results from the analysis of cyclic voltammograms (CVs) for the UPD and stripping of Cu on Pt DENs, and from experiments showing that the Pt core DENs catalyze the hydrogen evolution reaction before Cu UPD, but that after Cu UPD this reaction is inhibited. Results obtained by in-situ electrochemical X-ray absorption spectroscopy (XAS) confirm the core@shell structure. Calculations from density functional theory (DFT) show that the first portion of the Cu shell deposits onto the (100) facets, while Cu deposits lastly onto the (111) facets. The DFT-calculated energies for Cu deposition on the individual facets are in good agreement with the peaks observed in the CVs of the Cu UPD on the Pt DENs. Finally, structural analysis of Pt DENs having just partial Cu shells by in-situ XAS is consistent with the DFT-calculated model, confirming that the Cu partial shell selectively decorates the (100) facets. These results are of considerable significance because site-selective Cu deposition has not previously been shown on nanoparticles as small as DENs. In summary, the application of UPD as a synthetic route and characterization tool for core@shell DENs having well defined structures is established. A study of the degradation mechanism and degradation products of Pd DENs is provided as well. These DENs consisted of an average of 147 atoms per dendrimer. Elemental analysis and UV-vis spectroscopy indicate that there is substantial oxidation of the Pd DENs in air-saturated solutions, less oxidation in N₂-saturated solution, and no detectable oxidation when the DENs are in contact with H₂. Additionally, the stability improves when the DEN solutions are purified by dialysis to remove Pd²⁺-complexing ligands such as chloride. For the air- and N₂-saturated solutions, most of the oxidized Pd recomplexes to the interiors of the dendrimers, and a lesser percentage escapes into the surrounding solution. The propensity of Pd DENs to oxidize so easily is a likely consequence of their small size and high surface energy. Calculations from density functional theory (DFT) show that the first portion of the Cu shell deposits onto the (100) facets, while Cu deposits lastly onto the (111) facets. The DFT-calculated energies for Cu deposition on the individual facets are in good agreement with the peaks observed in the CVs of the Cu UPD on the Pt DENs. Finally, structural analysis of Pt DENs having just partial Cu shells by in-situ XAS is consistent with the DFT-calculated model, confirming that the Cu partial shell selectively decorates the (100) facets.
These results are of considerable significance because site-selective Cu deposition has not previously been shown on nanoparticles as small as DENs. In summary, the application of UPD as a synthetic route and characterization tool for core@shell DENs having well defined structures is established.
A study of the degradation mechanism and degradation products of Pd DENs is provided as well. These DENs consisted of an average of 147 atoms per dendrimer. Elemental analysis and UV-vis spectroscopy indicate that there is substantial oxidation of the Pd DENs in air-saturated solutions, less oxidation in N2-saturated solution, and no detectable oxidation when the DENs are in contact with H2. Additionally, the stability improves when the DEN solutions are purified by dialysis to remove Pd2+-complexing ligands such as chloride. For the air- and N2-saturated solutions, most of the oxidized Pd recomplexes to the interiors of the dendrimers, and a lesser percentage escapes into the surrounding solution. The propensity of Pd DENs to oxidize so easily is a likely consequence of their small size and high surface energy. / text
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Theoretical Physics of Dendrimers in Complex EnvironmentsWengenmayr, Martin 16 February 2021 (has links)
Verzweigte Strukturen in Makromolekülen eröffnen vielfältige Möglichkeiten zur gezielten topologischen Modifikation der Moleküle, neben chemischer Vielfalt und verschiedener Verarbeitung. Hochverzweigte Polymere bilden mehrere Klassen mit individuellen Eigenschaften, darunter Zimm-Stockmayer Polymere, fraktale Polymere und baumartig verzweigte Polymere, sogenannte Dendrimere. Die besondere Struktur hochverzweigter Polymere stellt eine große Anzahl funktionalisierbarer Endgruppen bereit, wodurch sie beispielsweise in lichtemittierenden Materialien, Beschichtungen, Haftmitteln und Biomaterialien Anwendung finden.
Dendrimere und dendritische Moleküle werden besonders im medizinischen Bereich als Wirkstofftransporter und Gen-Vektoren verwendet. Neben ihren Anwendungen, ist bei Dendrimeren die theoretische Beschreibung von besonderem Interesse. Ihre wohldefinierte, regelmäßige Verzweigungsstruktur wird nur von wenigen Parametern bestimmt, die Strukturen mit sehr unterschiedlichen Eigenschaften hervorbringt. Einzelne, isolierte Dendrimere wurden seit ihrer ersten Synthese 1978 intensiv theoretisch untersucht, doch wie sich Dendrimere in komplexen Umgebungen wie Polymerlösungen oder Polymerschmelzen verhalten, ist noch nicht hinreichend verstanden. Die vorliegende Arbeit leistet einen Beitrag zum theoretischen Verständnis der Konformationen und der Wechselwirkungen von Dendrimeren in polymerischem Lösungsmittel und linear-dendritischen Copolymeren in selektivem Lösungsmittel. Ziel der Arbeit ist die Erforschung der möglichen Zustände dieser Systeme mittels Computersimulationen und die Entwicklung und Validierung instruktiver, physikalischer Modelle.
Dendrimere in polymerischem Lösungsmittel zeigen Konformationen, die als gedrängt (crowded) bezeichnet werden und sich grundlegend von kollabierten oder Gaußschen Konformationen unterscheiden. Treffen mehrere Dendrimeren in einer Schmelze von chemisch kompatiblen linearen Polymeren zusammen, zeigen sie eine messbare Anziehungskraft zueinander, im Gegensatz zur rein repulsiven Wechselwirkung von Dendrimere in monomerischem gutem Lösungsmittel. Die Ursache für die Anziehungskraft wird mit umfangreichen Computersimulationen analysiert und mit etablierten Theorien sowie einer aus den Simulationserkenntnissen entwickelten Theorie verglichen. Ist die Mischung von Dendrimeren und linearen Polymeren in Kontakt mit einer undurchlässigen Wand, zeigen die Simulationsergebnisse eine deutliche Anziehungskraft zwischen Dendrimeren undWand, und es kommt zur Anreicherung der Dendrimere an der Oberfläche. Oberflächenanreicherungen von hochverzweigten Polymeren in einer Lösung von gleichartigen unverzweigten Polymeren wurden bereits in Extrusionsexperimenten nachgewiesen, was die Bedeutung der relativ schwachen entropischen Wechselwirkung für Industrieprozesse unterstreicht.
Werden lineare Ketten eines chemisch nicht kompatiblen Polymers auf die Endgruppen der Dendrimere aufgepfropft, entstehen linear-dendritische Copolymere, kurz Codendrimere. Die Funktionalisierung durch die Ketten verändert die Struktur des Dendrimers grundlegend. Codendrimere in selektivem Lösungsmittel zeigen eine Vielfalt an multimolekularen Strukturen, darunter auch multimolekulare Mizellen. Deren Strukturbildung wird detailliert untersucht und
theoretisch modelliert. Ein gutes Verständnis der Bildung von kleinen oder großen Clustern dieser Moleküle ist entscheidend um beispielsweise deren Löslichkeit oder deren Translokationsverhalten durch Poren oder Membranen beurteilen zu können, was etwa für medizinische Anwendungen relevant ist.:Abstract iii
1 Introduction 1
1.1 Motivation 1
1.2 Polymer Models 2
1.3 Dendrimers 3
1.3.1 Dendrimer Characteristics 3
1.3.2 Historic Overview and Synthesis 4
1.3.3 Overview of Theories and Simulations 5
1.4 Computer Simulation Methods 6
1.4.1 Monte Carlo Simulations 7
1.4.2 Bond Fluctuation Model 9
1.4.3 Implementation: LeMonADE 12
1.4.4 Observables Obtained by Simulations 14
2 Single Dendrimer 17
2.1 Theories and Models 17
2.2 Computer Simulations 19
2.2.1 Simulation Setup 19
2.2.2 Molecules Size and Shape 19
2.2.3 Density Profiles 21
2.2.4 Interactions Between a Dendrimer Pair 23
2.2.5 Interactions with a Purely RepulsiveWall 24
2.3 Summary 25
3 Conformations of Dendrimers in Linear Chain Solutions 27
3.1 Theories and Models 27
3.1.1 Mixtures of Star Polymers and Linear Chains 28
3.1.2 Mixtures of Zimm-Stockmayer Hyperbranched Polymers and Linear Chains 29
3.1.3 Dendrimers in Linear Polymer Melts: Mean Field Model 32
3.1.4 Scaling Approach for Linear Chain Solutions in Good Solvent 35
3.1.5 Dendrimers in Linear Polymer Solutions: Matching of Concentrations 36
3.1.6 Dendrimers in Linear Polymer Solutions: Matching of Length Scales 37
3.2 Computer Simulations 39
3.2.1 Simulation Setup 39
3.2.2 Dendrimer Size Scaling 39
3.2.3 Radial Monomer Distributions 44
3.3 Summary 48
4 Entropic Interactions of Dendrimers in Polymer Chain Melts 51
4.1 Theories and Models 51
4.1.1 Autophobicity 52
4.1.2 Depletion in Colloidal Systems 53
4.1.3 Depletion of Dendrimers in the Melt of Linear Chains 55
4.2 Computer Simulations 60
4.2.1 Simulation Setup 60
4.2.2 Interactions Between Dendrimers and Linear Chains 60
4.2.3 Pairwise Dendrimer Interaction 66
4.2.4 Interactions Between Dendrimers and Solid Walls 73
4.3 Summary 78
5 Linear-Dendritic Copolymers 81
5.1 Theories and Models 82
5.1.1 Multi-Core Micelles in Single Dendritic-Linear Copolymers 82
5.1.2 Multi-Molecular Micelles in Dilute Solutions of Dendritic-Linear Copolymers 83
5.2 Computer Simulation 91
5.2.1 Simulation Setup 91
5.2.2 Multi-Molecular Structures 93
5.2.3 Formation of Multi-Molecular Micelles 94
5.2.4 Structure Formation with Helmet like Codendrimers 100
5.2.5 Microphase Separation in the Melt 102
5.3 Summary 105
6 Summary and Outlook 107
Bibliography 111
Acknowledgements 119
List of Symbols 123
Erklärung 125 / Polymers with branched structures open a multitude of possibilities to tailor polymer materials beyond chemical and process based modifications. Polymers with a very high degree of branching are called hyperbranched polymers and can be grouped into different classes, for instance Zimm-Stockmayer hyperbranched, fractals, or regular tree like structures named dendrimers. Hyperbranched polymers provides a large number of functionalizeable terminal groups, that are used for various applications, for instance in light emitting materials, adhesives, coatings, and biomaterials.
Dendrimers and dendritic polymers are used in medical applications as drug delivery systems or gene vectors. Beside their applications, they are interesting from a theoretical point of view due to their well-defined, regular structure described by only a few parameters accessing a variety of structures with quite different properties. Individual dendrimers have been widely investigated theoretically, but so far little is known about dendrimers in more complex environments like polymer solutions or polymer melts. The main objective is the exploration of the phase states of these systems by coarse grained simulations and the development and validation of instructive physical models.
One prominent finding in this thesis is that conformations of dendrimers in the vicinity of chemically compatible polymer chains obey a special characteristic that is termed crowded conformations. Those conformations are fundamentally different from collapsed conformations or Gaussian conformations. With increasing volume fraction of the surrounding linear polymers, the interactions between dendrimers changes from purely repulsive in monomeric solvent to slightly attractive in a melt of sufficiently long polymer chains. The origin of the attractive interaction is investigated by large scale computer simulations and compared to different theoretical models. At an impenetrable wall, dendrimers immersed in a linear polymer melt display a significant attraction to the surface resulting in an accumulation of the dendrimers there. Surface accumulation of hyperbranched polymers in the melt of chemically compatible linear polymers has been found in extrusion experiments as well, pointing out the importance of the typically weak entropic interactions also for industrial processes.
Grafting functional groups to hyperbranched polymers does not only add a new feature to the polymers but also affects their overall structural properties. Dendrimers that are modified by grafting chemically different linear chains to the terminal groups result in linear-dendritic copolymers or simply codendrimers. With increasing volume fraction of codendrimers exposed to selective solvent, an enormous variety of multimolecular structures is formed. In particular, the formation of multimolecular micelles was found by computer simulations and successfully described by a mean field model. An in-depth understanding of the formation of small or large clusters of these molecules is important to estimate, for instance, their solubility or their translocation behavior through pores or membranes, which is highly relevant for medical applications.:Abstract iii
1 Introduction 1
1.1 Motivation 1
1.2 Polymer Models 2
1.3 Dendrimers 3
1.3.1 Dendrimer Characteristics 3
1.3.2 Historic Overview and Synthesis 4
1.3.3 Overview of Theories and Simulations 5
1.4 Computer Simulation Methods 6
1.4.1 Monte Carlo Simulations 7
1.4.2 Bond Fluctuation Model 9
1.4.3 Implementation: LeMonADE 12
1.4.4 Observables Obtained by Simulations 14
2 Single Dendrimer 17
2.1 Theories and Models 17
2.2 Computer Simulations 19
2.2.1 Simulation Setup 19
2.2.2 Molecules Size and Shape 19
2.2.3 Density Profiles 21
2.2.4 Interactions Between a Dendrimer Pair 23
2.2.5 Interactions with a Purely RepulsiveWall 24
2.3 Summary 25
3 Conformations of Dendrimers in Linear Chain Solutions 27
3.1 Theories and Models 27
3.1.1 Mixtures of Star Polymers and Linear Chains 28
3.1.2 Mixtures of Zimm-Stockmayer Hyperbranched Polymers and Linear Chains 29
3.1.3 Dendrimers in Linear Polymer Melts: Mean Field Model 32
3.1.4 Scaling Approach for Linear Chain Solutions in Good Solvent 35
3.1.5 Dendrimers in Linear Polymer Solutions: Matching of Concentrations 36
3.1.6 Dendrimers in Linear Polymer Solutions: Matching of Length Scales 37
3.2 Computer Simulations 39
3.2.1 Simulation Setup 39
3.2.2 Dendrimer Size Scaling 39
3.2.3 Radial Monomer Distributions 44
3.3 Summary 48
4 Entropic Interactions of Dendrimers in Polymer Chain Melts 51
4.1 Theories and Models 51
4.1.1 Autophobicity 52
4.1.2 Depletion in Colloidal Systems 53
4.1.3 Depletion of Dendrimers in the Melt of Linear Chains 55
4.2 Computer Simulations 60
4.2.1 Simulation Setup 60
4.2.2 Interactions Between Dendrimers and Linear Chains 60
4.2.3 Pairwise Dendrimer Interaction 66
4.2.4 Interactions Between Dendrimers and Solid Walls 73
4.3 Summary 78
5 Linear-Dendritic Copolymers 81
5.1 Theories and Models 82
5.1.1 Multi-Core Micelles in Single Dendritic-Linear Copolymers 82
5.1.2 Multi-Molecular Micelles in Dilute Solutions of Dendritic-Linear Copolymers 83
5.2 Computer Simulation 91
5.2.1 Simulation Setup 91
5.2.2 Multi-Molecular Structures 93
5.2.3 Formation of Multi-Molecular Micelles 94
5.2.4 Structure Formation with Helmet like Codendrimers 100
5.2.5 Microphase Separation in the Melt 102
5.3 Summary 105
6 Summary and Outlook 107
Bibliography 111
Acknowledgements 119
List of Symbols 123
Erklärung 125
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Polymer Assisted Dispersion of Carbon Nanotubes (CNTs) and Structure, Electronic Properties of CNT - Polymer CompositePramanik, Debabrata January 2017 (has links) (PDF)
Carbon nanotubes possess various unique and interesting properties. They have very high thermal and electrical conductivities, high stiffness, mechanical strength, and optical properties. Due to these properties, CNTs are widely used materials in a variety of fields. It is used for biotechnological and biomedical applications, as chemical and biosensor, in energy storage and field emission transistor. Experimentally synthesized CNTs are generally found in bundle form due to the strong vander Waals (vdW) at-traction between the individual tubes. To use CNTs in real life applications, we often require specific nanotubes with particular characteristics. The nanotube bundle is a mixture of various chirality, diameters and electronic properties (metallic and semiconducting). Only thermal energy is not sufficient to disperse nanotubes from the bundle geometry overcoming the strong vdW attraction between nanotubes. The hydrophobic and insoluble nature of CNTs in the aqueous medium makes the dispersion of CNTs even more difficult. So, it is a big challenge to get single pristine nanotube from the bundle geometry.
Many experimental and theoretical studies have addressed the problem of nanotube dispersion from the bundle geometry. Ultrasonic dispersing method is a widely used technique for this purpose where ultrasonic sound is applied to agitate particles in a system. Other methods include using different organic and inorganic solutions, various surfactant molecules, different polymers as dispersing agents. In this study we extend our e orts to develop some better methods and improved dispersing agents. In this thesis, we address the problem of CNT dispersion. To address this issue, we rst give a quantitative estimation of the effective interaction between nanotubes. Next, we introduce different polymers (ssDNA and dendrimers) as external agents and show that they help to overcome the strong adhesive interaction between CNTs and make nanotube dispersion possible from the bundle geometry. For all of the works presented in this thesis, we have used fully atomistic MD simulation and DFT level calculations. We study ssDNA-CNT complex using all-atom MD simulation and calculate various structural quantities to show the stability of ssDNA-CNT complex in aqueous medium. The adsorption of ssDNA bases on CNT surface is driven by - interaction between nucleic bases and CNT. Using the potential of mean forces (PMF) calculation, we study the binding strength of the polynucleotide ssDNA for poly A, T, G, and C with CNT of chirality (6,5). From the PMF calculation, we show the binding sequence to be A > T > C > G. Except for poly G, our result is in good agreement with earlier reported single molecule force spectroscopy results where the sequence of binding interaction was reported to be A > G > T > C. To explore how the interaction between two CNTs mod-i ed in presence of ssDNA between them, we perform PMF calculation between the two ssDNA-wrapped CNTs. The PMF shows the sequence of interaction strength between two ssDNA-wrapped CNTs for different nucleic bases to be T > A > C > G. Thus, from PMF calculations we show the poly T to have the highest dispersion efficiency, which is consistent with earlier reported experimental study. Our PMF calculation shows that poly C and poly G reduce the attraction between two CNTs drastically, whereas poly A and poly T make the interaction fully repulsive in nature. We also present microscopic pictures of the various binding conformations for ssDNA adsorbed on CNT surface.
We also study the dendrimer-CNT complex for both the PAMAM and PETIM dendrimers of different generations at various protonation states and present microscopic pictures of the complex. We calculate PMF between two dendrimer wrapped CNTs and show that protonated and higher generations (G3, G4, and so forth) non-protonated PAMAM dendrimers can be used as e ective agents to disperse CNTs from bundle geometry. We also study the chirality dependence of PMF respectively.
Finally, we study the interaction of mannose dendrimer with CNTs and show that the wrapping of mannose dendrimer can drive a metal to semiconducting transition in a metallic CNT. We attribute the carbon-carbon bond length assymetry in CNT due to the wrapping of mannose dendrimer as the reason for this band gap opening which leads to metal-semiconductor transition in CNT. Thus, the wrapping of mannose dendrimer on CNT can change its electronic properties and can be used in the band gap engineering of CNT in future nanotechnology.
Thus, the works carried out here in this dissertation will help to address the problem of nanotube dispersion from the bundle geometry which will in turn help to use CNT for various applications in diverse fields.
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Inorganic Aspects of “Click” Chemistry in Polymers and Dendrimers : synthesis, Nanoparticle Stabilization and Catalysis / Aspects inorganiques de la chimie “click” dans les polymères et dendrimères : synthèses, stabilisation de nanoparticules et catalyseLiang, Liyuan 06 July 2011 (has links)
La thèse concerne les aspects inorganiques de la réaction des alcynes terminaux avec les azotures, la principale des réactions dites ”click”. La catalyse de cette réaction par des dendrimères centrés sur le cuivre (I) nous a permis de mettre en évidence des effets dendritiques originaux. Les assemblages dendritiques et polymériques fonctionnels réalisés à l’aide cette réaction “click”, en particulier avec des carboranes, nous ont conduits à la stabilisation de nanoparticules d’or et de palladium à partirde cations coordonnés aux triazoles “click”. La catalyse très efficace dans aqueux milieu et dans les conditions ambiantes de formation de liaison carbone-carbone a été réalisée à l’aide de très faibles quantités de ces nanoparticulesde palladium stabilisées. / The thesis concerns aspects of inorganic reaction between organic azides and terminal alkynes, the main “click” reactions. Catalysis of this reaction by copper (I)-centered dendrimers allowed us to highlight the dendritic effects originals. The dendritic and polymeric functional assemblies produced using the "click" reaction, especially with carboranes, led us to the stabilization of gold nanoparticles and palladium from cation-coordinated "click" triazole. The highly efficient catalysis in aqueous medium under ambient conditions of formation of carbon-carbon was carried out using very small amounts of stabilized palladium nanoparticles.
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SYNTHESIS AND CHARACTERIZATION OF DOXORUBICIN CARRYING CETUXIMAB-PAMAM DENDRIMER BIOCONJUGATESSAXENA, GUNJAN 26 April 2012 (has links)
A tumor targeted dendrimer based drug delivery system was designed and synthesized to carry chemotherapy drug doxorubicin. Polyamidoamine (PAMAM) dendrimer G4.5 was chosen as the underlying carrier. Anionic G4.5 is a good option for drug delivery as it consists of 128 surface groups, is less cytotoxic and favorably biodistributed. The delivery system was synthesized using a layer-by layer arrangement of three functional entities: chemotherapy drug doxorubicin, monoclonal antibody Cetuximab against EGF receptor, and polyethylene glycol (PEG). Doxorubicin was attached via an acid-sensitive hydrazon linkage to the dendrimer. Macromolecules are taken in by cells through endocytosis. pH inside the early endosomes to lysosomes ranges from pH 6 to 4.5. These acidic conditions are favorable for release of drug bound to the dendrimer vehicle through acid-sensitive linkage. 35% of all solid tumors of brain express exceptionally high EGF receptors whereas normal brain tumors express less EGFR. This makes the EGFR a potent targeting moiety for targeted drug delivery. Cetuximab will serve as a targeting ligand to help the delivery system target tumor cells. PEG was incorporated as a linker between Cetuximab and dendrimer to avoid reticuloendothelial system (RES) uptake of the system, increase biocompatibility, increase drug half-life and other shortcomings associated with nanomaterials. Nuclear magnetic resonance spectroscopy (NMR), fluorescence anisotropy, and western blotting were used to confirm the conjugation of PEG, doxorubicin and cetuximab to the dendrimer. The synthesized delivery system was characterized using ultraviolet-visible spectroscopy (UV-Vis) to approximate the number of doxorubicin attached. Dynamic light scattering (DLS) and zeta potential were used to analyze the change in size and surface properties of dendrimer during the synthesis. Doxorubicin release studies were conducted at different pHs. Maximum doxorubicin was released at pH 4.5 indicating the successful acid-sensitive linkage between the drug and dendrimer. Cytotoxicity studies indicated that the addition of PEG increased the biocompatibility as compared to free doxorubicin whereas; combination of doxorubicin and cetuximab exerted a significant toxic effect over a period of 72 hours. The cellular uptake of the delivery system was higher than that of free doxorubicin. Free DOX localized mainly in the nucleus whereas, CTX-G4.5-PEG-DOX conjugate localized within both cytoplasm and nucleus after 6 hour incubation. The synthesized delivery system represents a potential targeted drug delivery system.
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Synthesis and Characterization of Clickable Dendrimer Hydrogels for Ocular Drug DeliveryTian, Jingfei 28 April 2014 (has links)
Topical medication is a standard treatment for glaucoma. However, frequent dosing makes the therapy inconvenient and patient unfriendly. There is a great need to develop new topical formulations that provide long lasting noninvasive drug release. In this thesis, novel clickable dendrimer hydrogels for anti-glaucoma drug delivery were synthesized and characterized. Polyamidoamine (PAMAM) dendrimers have been widely applied for drug delivery. The physical characteristics they possess include monodispersity, water solubility, encapsulation ability, and a large number of surface groups. Polycationic PAMAM dendrimer G3 was surface modified with alkyne-PEG5-acid and then reacted with polyethylene glycol bisazide (PEG-BA, 1100 gmol-1) through click chemistry to form a cross-linked hydrogel. The resulting hydrogels were characterized in terms of mechanical properties, swelling, structural morphology, pH-dependent degradation, anti-glaucoma drugs (brimonidine tartrate and timolol maleate) release and cytotoxicity. To fully explore PAMAM dendrimers to make clickable hydrogels, polyanionic PAMAM dendrimer G4.5 was also surface modified with propargylamine to possess alkyne groups and successfully formed a hydrogel with PEG-BA. The work conducted in the thesis shows that clickable dendrimer hydrogels were successfully developed and shown to possess desired properties for delivery of anti-glaucoma drugs.
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Engineering of Polyamidoamine Dendrimers for Cancer TherapyXu, Leyuan 01 January 2015 (has links)
Dendrimers are a class of polymers with a highly branched, three-dimensional architecture comprised of an initiator core, several interior layers of repeating units, and multiple active surface terminal groups. Dendrimers have been recognized as the most versatile compositionally and structurally controlled nanoscale building blocks for drug and gene delivery. Polyamidoamine (PAMAM) dendrimers have been most investigated because of their unique structures and properties. Polycationic PAMAM dendrimers form compacted polyplexes with nucleic acids at physiological pH, holding great potential for gene delivery.
Folate receptor (FRα) is expressed at very low levels in normal tissues but expressed at high levels in cancers in order to meet the folate demand of rapidly dividing cells under low folate conditions. Our primary aim was to investigate folic acid (FA)-conjugated PAMAM dendrimer generation 4 (G4) conjugates (G4-FA) for targeted gene delivery. The in vitro cellular uptake and transfection efficiency of G4-FA conjugates and G4-FA/DNA polyplexes were investigated in Chapter 4. It was found the cellular uptake of G4-FA conjugates and G4-FA/DNA polyplexes was in a FR-dependent manner. Free FA competitively inhibited the cellular uptake of G4-FA conjugates and G4-FA/DNA polyplexes. G4-FA/DNA polyplexes were preferentially taken up by FR-positive HN12 cells but not FR-negative U87 cells. In contrast, the cellular uptake of G4 dendrimers and G4/DNA polyplexes was non-selective via absorptive endocytosis. G4-FA conjugates significantly enhanced cytocompatibility and transfection efficiency compared to G4 dendrimers. This work demonstrates that G4-FA conjugates allow FR-targeted gene delivery, reduce cytotoxicity, and enhance gene transfection efficiency.
The in vivo biodistribution of G4-FA conjugates and anticancer efficacy of G4-FA/siRNA polyplexes were investigated in Chapter 5. Vascular endothelial growth factor A (VEGFA) is one of the major regulators of angiogenesis, essential for the tumor development. It was found G4-FA/siVEGFA polyplexes significantly knocked down VEGFA mRNA expression and protein release in HN12 cells. In the HN12 tumor-bearing nude mice, G4-FA conjugates were preferentially taken up by the tumor and retained in the tumor for at least 21 days following intratumoral (i.t.) administration. Two-dose i.t. administration of G4-FA/siVEGFA polyplexes significantly inhibited tumor growth by lowering tumor angiogenesis. In contrast, two-dose i.t. administration of G4/siVEGFA polyplexes caused severe skin lesion, presumably as a result of local toxicity. Taken together, this work shows great potential for the use of G4-FA conjugates in targeted gene delivery and cancer gene therapy.
We also explored polyanionic PAMAM dendrimer G4.5 as the underlying carrier to carry camptothecin (CPT) for glioblastoma multiforme therapyin Chapter 6. "Click" chemistry was applied to improve polymer-drug coupling reaction efficiency. The CPT-conjugate displayed a dose-dependent toxicity with an IC50 of 5 μM, a 185-fold increase relative to free CPT, presumably as a result of slow release. The conjugated CPT resulted in G2/M arrest and cell death while the dendrimer itself had little to no toxicity. This work indicates highly efficient "click" chemistry allows for the synthesis of multifunctional dendrimers for sustained drug delivery.
Immobilizing PAMAM dendrimers to the cell surface may represent an innovative method of enhancing cell surface loading capacity to deliver therapeutic and imaging agents. In Chapter 7, macrophage RAW264.7 (RAW) was hybridized with PAMAM dendrimer G4.0 (DEN) on the basis of bioorthogonal chemistry. Efficient and selective cell surface immobilization of dendrimers was confirmed by confocal microscopy. It was found the viability and motility of RAW-DEN hybrids remained the same as untreated RAW cells. Furthermore, azido sugar and dendrimer treatment showed no effect on intracellular AKT, p38, and NFκB (p65) signaling, indicating that the hybridization process neither induced cell stress response nor altered normal signaling. This work shows the feasibility of applying bioorthogonal chemistry to create cell-nanoparticle hybrids and demonstrates the noninvasiveness of this cell surface engineering approach.
In summary, these studies indicate surface-modification of PAMAM dendrimer G4 with FA can effectively target at FR-positive cells and subsequently enhance in vitro transfection efficiency and in vivo gene delivery. G4-FA conjugates may serve as a versatile targeted gene delivery carrier potentially for cancer gene therapy. PAMAM dendrimers G4.5 may serve as a drug delivery carrier for the controlled release of chemotherapeutics. The immune cell-dendrimer hybrids via bioorthogonal chemistry may serve as an innovative drug and gene delivery carrier potentially for cancer chemotherapy. Taken together, engineering of PAMAM dendrimers may advance anticancer drug and gene delivery.
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