We study the conformational change of insulin fibril growth from three aspects: the impact of (i) incubation time; (ⅱ) nano-particles; (iii) and ion added. We used circular dichroism (CD) spectroscopy and fourier transform infrared spectroscopy (FT-IR) to obtain the structural transition of the insulin, and gain the morphology information of fibril by atomic force microscopy (AFM) and transmission electron microscopy (TEM). We show that the insulin transform from £\-helix to £]-sheet structure as increased incubated time. The addition of Au nanoparticles (NPs) caused the formation of coordination bond with insulin fiber and produced shorter and thicker insulin fibril . The Fe3O4 NPs, on the other hand, offered only van der Waals interaction toward insulin fibril. Hence they could be used to separate insulin fibril from solution. Finally, addition of salts can induce the conformation changes of insulin fibril ten times faster than that without salts. And the insulin fibril fragment was two or three times shorter than that produced without salts. At high salt concentration, insulin formed amorphous aggregates. This phenomenon was attribute to anions from salt: covering the surface charge of insulin fibril, they weaken the original electrostatic repulsion among insulin fibrils and result in their aggregation.

As a part of a larger effort towards the fundamental understanding of mechanical behaviors of polymers toughened by nanoparticles, this dissertation focuses on the structure-property relationship of epoxies modified with nano-sized poly(ethylene-altpropylene)- b-poly(ethylene oxide) (PEP-PEO) block copolymer (BCP) micelle particles. The amphiphilic BCP toughener was incorporated into a liquid epoxy resin and selfassembled into well-dispersed 15 nm spherical micelle particles. The nano-sized BCP, at 5 wt% loading, can significantly improve the fracture toughness of epoxy (ca. 180% improvement) without reducing modulus at room temperature and exhibits only a slight drop (ca. 5 �C) in glass transition temperature (Tg). The toughening mechanisms were found to be BCP micelle nanoparticle cavitation, followed by matrix shear banding, which mainly accounted for the observed remarkable toughening effect. The unexpected ?nano-cavitation? phenomenon cannot be predicted by existing physical models. The plausible causes for the observed nano-scale cavitation and other mechanical behaviors may include the unique structural characteristics of BCP micelles and the influence from the surrounding epoxy network, which is significantly modified by the epoxy-miscible PEO block. Other mechanisms, such as crack tip blunting, may also play a role in the toughening. Structure-property relationships of this nano-domain modified polymer are discussed. In addition, other important factors, such as strain rate dependence and matrix crosslink density effect on toughening, have been investigated. This BCP toughening approach and conventional rubber toughening techniques are compared. Insights on the decoupling of modulus, toughness, and Tg for designing high performance thermosetting materials with desirable physical and mechanical properties are discussed.

none

With the given information that dendrimers have precisely controlled their sizes and spherical structures in the molecular level, the aim of this study is to show that dendrimer particles can become ordered into a self-assembled regular structure due to the nature of their regular sizes and shapes. For this project, melamine based generation 3 dendrimer was used for solution cast of thin films from the dendrimer-chloroform solutions with different casting conditions, i.e. various solution concentrations, casting temperatures, and substrates. As a result of these experiments, unique phenomena of highly ordered uniform 2-D contraction separations were observed during the solvent evaporation from the dendrimer films. The cast films from the concentration of 0.8 wt% and higher exhibit regular 2-D separation contraction patterns and make well-developed regularly arrayed structures due to the interaction between the contraction stresses and adhesion strength between films and substrates. From the DSC tests, both powder and cast film samples of a dendrimer show similar melting behaviors with different areas under the melting peaks. The results of these tests show that dendrimers, when they are in a descent environment that provides dendrimers with molecular mobility due to surface ionic bonding strength, can make a structural order and regularity in their macroscopic structures.

none

The unique properties of engineered nanoparticles have many potential applications in oil reservoirs, e.g., as emulsion stabilizers for enhanced oil recovery, or as nano-sensors for reservoir characterization. Long-distance propagation (>100 m) is a prerequisite for many of these applications. With diameters between 10 to 100 nanometers, nanoparticles can easily pass through typical pore throats in reservoirs, but physicochemical interaction between nanoparticles and pore walls may still lead to significant retention. A model that accounts for the key mechanisms of nanoparticle transport and retention is essential for design purposes. In this dissertation, interactions are analyzed between nanoparticles and solid surface for their effects on nanoparticle deposition during transport with single-phase flow. The analysis suggests that the DLVO theory cannot explain the low retention concentration of nanoparticles during transport in saturated porous media. Moreover, the hydrodynamic forces are not strong enough for nanoparticle removal from rough surface. Based on different filtration mechanisms, various continuum transport models are formulated and used to simulate our nanoparticle transport experiments through water-saturated sandpacks and consolidated cores. Every model is tested on an extensive set of experimental data collected by Yu (2012) and Murphy (2012). The data enable a rigorous validation of a model. For a set of experiments injecting the same kind of nanoparticle, the deposition rate coefficients in the model are obtained by history matching of one effluent concentration history. With simple assumptions, the same coefficients are used by the model to predict the effluent histories of other experiments when experimental conditions are varied. Compared to experimental results, colloid filtration model fails to predict normalized effluent concentrations that approach unity, and the kinetic Langmuir model is inconsistent with non-zero nanoparticle retention after postflush. The two-step model, two-rate model and two-site model all have both reversible and irreversible adsorptions and can generate effluent histories similar to experimental data. However, the two-step model built based on interaction energy curve fails to fit the experimental effluent histories with delay in the leading edge but no delay in the trailing edge. The two-rate model with constant retardation factor shows a big failure in capturing the dependence of nanoparticle breakthrough delay on flow velocity and injection concentration. With independent reversible and irreversible adsorption sites the two-site model has capability to capture most features of nanoparticle transport in water-saturated porous media. For a given kind of nanoparticles, it can fit one experimental effluent history and predict others successfully with varied experimental conditions. Some deviations exist between model prediction and experimental data with pump stop and very low injection concentration (0.1 wt%). More detailed analysis of nanoparticle adsorption capacity in water-saturated sandpacks reveals that the measured irreversible adsorption capacity is always less than 35% of monolayer packing density. Generally, its value increases with higher injection concentration and lower flow velocities. Reinjection experiments suggest that the irreversible adsorption capacity has fixed value with constant injection rate and dispersion concentration, but it becomes larger if reinjection occurs with larger concentration or smaller flow rate. / text

Targeted delivery of drugs to specific regions of the body, or even to specific regions of the cell, promises enhanced drug efficacy and reduced systemic toxicity. By covalently coupling targeting ligands, the smart drug delivery systems are capable of targeting specific cell types exclusively through ligand-receptor interactions. The main goal of the project is to create a polymeric nanoparticle drug delivery system from synthesized biodegradable polymers and modify the polymeric nanoparticles using targeting antibodies for targeted delivery of anticancer drugs. A new biodegradable copolymer poly(2-methyl, 2-carboxy trimethylene carbonate-co-D,L-lactide)-graft-poly(ethylene glycol)-furan (poly(TMCC-co-LA)-g-PEG-furan) was synthesized and characterized. The copolymers self-assembled into spherical nanoparticles in aqueous environments with the hydrodynamic diameters controlled over a broad size range. Immuno-polymeric nanoparticles were created by coupling maleimide-modified anti-human epidermal growth factor receptor 2 (anti-HER2) antibodies to the self-assembled nanoparticles through Diels-Alder (DA) chemistry. This new coupling methodology was demonstrated to be relatively rapid, highly efficient and specific under mild conditions. In vitro studies showed that the immuno-nanoparticles bound specifically and efficiently with SKBR3 breast cancer cells that overexpress HER2 receptors. Anticancer drugs were incorporated into the immuno-nanoparticle system and the drug delivery via an antibody-mediated targeting mechanism was investigated in vitro. First, a protein anticancer drug, interleukin-2 (IL-2), was physically encapsulated through polymer-drug association. The IL-2 encapsulated anti-HER2 immuno-nanoparticles exhibited a cell-binding associated IL-2 release in the extracellular space upon binding with HER2-overexpressing SKBR3 breast cancer cells. Second, a small molecule hydrophobic drug, doxorubicin (DOX), was chemically conjugated on the nanoparticle surface after the antibody coupling, using the same DA chemistry. The novel formulation localized DOX in the cell nucleus of HER2-overexpressing SKBR3 breast cancer cells and remained the biological function of conjugated DOX. Compared to the nanoparticles bearing DOX or anti-HER2 antibody alone, the nanoparticles having a combination of DOX and anti-HER2 antibody exhibited the most significant cytotoxicity and specificity against SKBR3 cells relative to healthy HMEC-1 endothelial cells, demonstrating the potential of the DOX-immuno-nanoparticles as a novel platform for intracellular DOX delivery. This work provides a novel means for the delivery of combination immunotherapy/chemotherapy to more effectively treat certain malignancies.

Targeted delivery of drugs to specific regions of the body, or even to specific regions of the cell, promises enhanced drug efficacy and reduced systemic toxicity. By covalently coupling targeting ligands, the smart drug delivery systems are capable of targeting specific cell types exclusively through ligand-receptor interactions. The main goal of the project is to create a polymeric nanoparticle drug delivery system from synthesized biodegradable polymers and modify the polymeric nanoparticles using targeting antibodies for targeted delivery of anticancer drugs. A new biodegradable copolymer poly(2-methyl, 2-carboxy trimethylene carbonate-co-D,L-lactide)-graft-poly(ethylene glycol)-furan (poly(TMCC-co-LA)-g-PEG-furan) was synthesized and characterized. The copolymers self-assembled into spherical nanoparticles in aqueous environments with the hydrodynamic diameters controlled over a broad size range. Immuno-polymeric nanoparticles were created by coupling maleimide-modified anti-human epidermal growth factor receptor 2 (anti-HER2) antibodies to the self-assembled nanoparticles through Diels-Alder (DA) chemistry. This new coupling methodology was demonstrated to be relatively rapid, highly efficient and specific under mild conditions. In vitro studies showed that the immuno-nanoparticles bound specifically and efficiently with SKBR3 breast cancer cells that overexpress HER2 receptors. Anticancer drugs were incorporated into the immuno-nanoparticle system and the drug delivery via an antibody-mediated targeting mechanism was investigated in vitro. First, a protein anticancer drug, interleukin-2 (IL-2), was physically encapsulated through polymer-drug association. The IL-2 encapsulated anti-HER2 immuno-nanoparticles exhibited a cell-binding associated IL-2 release in the extracellular space upon binding with HER2-overexpressing SKBR3 breast cancer cells. Second, a small molecule hydrophobic drug, doxorubicin (DOX), was chemically conjugated on the nanoparticle surface after the antibody coupling, using the same DA chemistry. The novel formulation localized DOX in the cell nucleus of HER2-overexpressing SKBR3 breast cancer cells and remained the biological function of conjugated DOX. Compared to the nanoparticles bearing DOX or anti-HER2 antibody alone, the nanoparticles having a combination of DOX and anti-HER2 antibody exhibited the most significant cytotoxicity and specificity against SKBR3 cells relative to healthy HMEC-1 endothelial cells, demonstrating the potential of the DOX-immuno-nanoparticles as a novel platform for intracellular DOX delivery. This work provides a novel means for the delivery of combination immunotherapy/chemotherapy to more effectively treat certain malignancies.

No description available.

<p>The particles of the Pt metal were well dispersed on carbon nanotubes when EG was used and in isopropanol poor dispersion was observed and no further investigation was done on them. The platinum wt% on the supports observed from EDS was 21.8, 19.10 and 16.74wt% for Pt/EMWCNT, Pt/LPGCNT and Pt/ commercial CNT respectively. Pt/LPGMWCNT showed high electro-catalytic activity of 2.48 mA and active surface area of 76 m2/g, toward oxygen reduction, observed from cyclic voltammogram in iv sulfuric acid. Pt/LPGMWCNT also showed better tolerance toward methanol, however it was not highly active towards methanol, and hence the methanol oxidation peak current observed between 0.75 and 08 potential was the smallest. In this study a wide range of instruments was used to characterize the properties and behavior of Platinum nanoparticles on multi-wall carbon nanotubes. To add to the already mentioned, Scanning electrochemical microscopy (SEM), proton induced x-ray emission (PIXE), scanning electrochemical microscopy (SECM) and Brunauer-Emmett Tellar (BET) were also used.</p>