Synthetic glycopeptides have attracted much interest in the biomedical field due to their structural similarities to the natural glycopeptides or glycoproteins. It is still difficult to synthesize glycopeptides with greater efficiency and ring opening polymerization remains an effective way to do so. Proteoglycans are a special class of glycoproteins with glycosaminoglycan chains. In this study, I tried to do controlled ring opening polymerization of Hyaluronic acid derivatives with smaller to higher molecular weight while avoiding side reactions. It is challenging to work with higher molecular weight molecules and do a click reaction in water effectively. Making nanopolymers with a desired size, studies of the characteristics, and how to build nanocarriers for drug delivery application was the focus of this work. Polymeric characteristics, e.g., modification and polymer formation were studied by nuclear magnetic resonance technique; Particle size was studied by dynamic light scattering and the loading of rhodamine B encapsulated into the polymer was measured by confocal imaging technique.

Magnetic force microscopy (MFM) is a widely-used technique for measuring the local magnetic properties of a variety of materials. This method covers a large fi eld of applications ranging from fundamental research of micro-magnetic phenomena to industrial applications in the development of magnetic recording components. The image formation in MFM measurements is based on the magneto-static interaction of a sharp magnetic tip with the probed sample. Despite the fact that MFM is quite easy to perform, image interpretation remains challenging. This is due to the accurate characterization of the probing tip that is needed for a quantitative interpretation of the MFM data in terms of the local magnetic properties of the sample. This thesis examines the fabrication and utilization of special MFM probes based on single ferromagnetic nanoparticles as the magnetically interacting element. A magnetic probe that consists of a very small magnetic single-domain particle can be accurately described by a magnetic point dipole. Such a probe potentially yields an improved lateral resolution and a simplifi ed quantitative interpretation of MFM images compared to a standard thin-fi lm coated MFM tip. First of all, one part of this thesis examines the fabrication of suitable single-domain particles. In particular, this part is focussed on experiments concerning the protection of these particles from oxidation in ambient conditions. To this end, these ferromagnetic particles were coated with gold using the light-induced deposition of gold in a photoactive metal-salt solution. The chemical surface passivation of the particles by the gold coating was verifi ed using diff erent techniques (SQUID, MFM). In the next step, these particles were mechanically affi xed to a standard silicon tip of atomic force microscopy (AFM). The controlled attachment of a single particle, as well as the attachment of multiple particles to such a Si-AFM tip was demonstrated. Another part of the thesis examines the magnetic imaging with particle based probes in MFM experiments. A minimum of four cobalt particles affi xed to the tip was determined as the threshold for obtaining a reasonable MFM signal. It was possible to image the magnetic domain structure of a hard disk drive sample with these particle probes. Using a simulation of the MFM data, the orientation and the position of the e ffective tip dipole were determined. The e ffective dipole moment of the tip is found by a calibration experiment assuming a magnetic dipole-dipole interaction between the tip and another magnetic particle.

Nanometer-scale silicon shows extraordinary electronic and optical properties that are not available for bulk silicon, and many investigations toward applications in optoelectronic devices are being pursued. Silicon nanoparticle films made from solution are a promising candidate for low-cost solar cells. However, controlling the properties of silicon nanoparticles is quite a challenge, in particular shape and size distribution, which effect device performance. At present, none of the solar cells made from silicon nanoparticle films have an efficiency exceeding the efficiency of those based on crystalline silicon. To address the challenge of controlling silicon nanoparticle properties, both theoretical and experimental investigations are needed. In this thesis, we investigate silicon nanoparticle properties via quantum mechanical modeling of silicon nanoparticles and synthesis of silicon nanoparticle films via colloidal grinding. Silicon nanoparticles with shapes including cubic, rectangular, ellipsoidal and flat disk are modeled using semi-empirical methods and configuration interaction. Their electronic properties with different surface passivation were also studied. The results showed that silicon nanoparticles with hydrogen passivation have higher HOMOLUMO gaps, and also the HOMO-LUMO gap depends on the size and the shape of the particle. In contrast, silicon nanoparticles with oxygen passivation have a lower HOMO-LUMO gap. Raman spectroscopy calculation of silicon nanoparticles show peak shift and asymmetric broadening similar to what has been observed in experiment. Silicon nanoparticle synthesis via colloidal grinding was demonstrated as a straightforward and inexpensive approach for thin film solar cells. Data analysis of silicon particles via SEM images demonstrated that colloidal grinding is effective in reducing the Si particle size to sub-micron in a short grinding time. Further increases in grinding time, followed by filtration demonstrated a narrowing of the Si particle size and size-distribution to an average size of 70 nm. Raman spectroscopy and EDS data demonstrated that the Si nanoparticles contain oxygen due to exposure to air during grinding. I-V characterization of the milled Si nanoparticles showed an ohmic behaviour with low current at low biases then Schottky diode behaviour or a symmetric curve at large biases. / Graduate / 0794 / 0544 / zahraalbu@hotmail.com

<p>The rapidly increasing use of silver nanoparticles (Ag NPs) in consumer products and medical applications has raised ecological and human health concerns. Significant progress has been made in understanding the toxicity of silver nanoparticles (Ag NPs) under carefully controlled laboratory conditions. The goals of this dissertation were to investigate the mechanism of Ag NP toxicity under both laboratory conditions and environmental backgrounds, using <italic>Caenorhabditis elegans</italic> (<italic>C. elegans</italic>) as a model system. A key question for addressing these concerns is whether Ag NP toxicity is mechanistically unique to nanoparticulate silver or if it is a result of the release of silver ions. Ag NPs are produced in a large variety of monomer sizes and coatings, and since their physicochemical behavior depends on the media composition, it is important to understand how these variables modulate toxicity.</p><p> In order to test the hypothesis of a particle-specific effect, multiple techniques were used, including analytical chemistry, pharmacological rescue, and genetic analysis. Results suggested that dissolution was important for all tested Ag NPs and oxidative stress (a particle-specific effect) was important only for some Ag NPs, especially the citrate-coated Ag NPs (CIT-Ag NPs). The hypothesis of the particle-specific effect was further tested by investigating the cellular uptake and damage co-localization upon exposures to CIT-Ag NPs. I found that Ag NPs crossed all layers, including the pharynx, gut, and also embryos through trans-generational transfer. Sites of damage were examined through transmission electron microscopy (TEM), and CIT-Ag NPs showed a more severe and deeper level of damage compared to ionic Ag. In addition, pharmacological inhibitors in parallel with genetic mutants (deficient in both endocytosis and lysosomal function) were used to explore the impact of those pathways on Ag NP uptake and associated toxicity. I found that endocytosis was important for CIT-Ag NP uptake and toxicity. Most intriguingly, one of the lysosomal deficient mutants was much more sensitive than wild type to reproductive inhibition after exposure to CIT-Ag NPs but not ionic Ag, constituting a clear nanoparticle-specific toxic effect.</p><p> These laboratory mechanistic studies, however, cannot be directly extrapolated to complicated environmental conditions, including variable amounts of natural organic matter (NOM), different temperatures and salinities, surface sulfidation, etc. My general hypothesis was that complex environmental medium would reduce Ag NP toxicity. In support of this, the environmental conditions present in mesocosms resulted in a loss of toxicity one week after dosing/spiking. In laboratory studies, I found that that increasing temperature and salinity tended to increase Ag NP toxicity, while sulfidation reduced Ag NP toxicity, acting as a &ldquonatural antidote&rdquo. I studied two types of NOM, Suwannee River and Pony Lake fulvic acids (SRFA and PLFA respectively). PLFA rescued toxicity more effectively than SRFA. Therefore, CIT-Ag NP-NOM interactions were explored in depth using PLFA. Using hyperspectral dark field microscopy, I was able to detect the formation of Ag NP-PLFA complexes and the limited tissue uptake of Ag NPs (with and without PLFA). Consistent with the reduced acute toxicity of Ag NPs by PLFA, I also found a rescue effect of PLFA on Ag NP-induced ultrastructural damage.</p><p> In conclusion, Ag NP toxicity resulted largely from dissolution and in some cases also from a particle-specific effect. However, Ag NP toxicity was strongly altered by environmental matrices. Continued in depth elucidation of Ag NP behavior, cellular uptake pathways and trafficking, and their interactions with other environmental factors will be invaluable in predicting, designing, and remediating the potential/existing environmental implications of silver-related nanotechnology.</p> / Dissertation

Nanometer-scale silicon shows extraordinary electronic and optical properties that are not available for bulk silicon, and many investigations toward applications in optoelectronic devices are being pursued. Silicon nanoparticle films made from solution are a promising candidate for low-cost solar cells. However, controlling the properties of silicon nanoparticles is quite a challenge, in particular shape and size distribution, which effect device performance. At present, none of the solar cells made from silicon nanoparticle films have an efficiency exceeding the efficiency of those based on crystalline silicon. To address the challenge of controlling silicon nanoparticle properties, both theoretical and experimental investigations are needed. In this thesis, we investigate silicon nanoparticle properties via quantum mechanical modeling of silicon nanoparticles and synthesis of silicon nanoparticle films via colloidal grinding. Silicon nanoparticles with shapes including cubic, rectangular, ellipsoidal and flat disk are modeled using semi-empirical methods and configuration interaction. Their electronic properties with different surface passivation were also studied. The results showed that silicon nanoparticles with hydrogen passivation have higher HOMOLUMO gaps, and also the HOMO-LUMO gap depends on the size and the shape of the particle. In contrast, silicon nanoparticles with oxygen passivation have a lower HOMO-LUMO gap. Raman spectroscopy calculation of silicon nanoparticles show peak shift and asymmetric broadening similar to what has been observed in experiment. Silicon nanoparticle synthesis via colloidal grinding was demonstrated as a straightforward and inexpensive approach for thin film solar cells. Data analysis of silicon particles via SEM images demonstrated that colloidal grinding is effective in reducing the Si particle size to sub-micron in a short grinding time. Further increases in grinding time, followed by filtration demonstrated a narrowing of the Si particle size and size-distribution to an average size of 70 nm. Raman spectroscopy and EDS data demonstrated that the Si nanoparticles contain oxygen due to exposure to air during grinding. I-V characterization of the milled Si nanoparticles showed an ohmic behaviour with low current at low biases then Schottky diode behaviour or a symmetric curve at large biases. / Graduate / 0794 / 0544 / zahraalbu@hotmail.com

The interactions between the immune and nervous systems play an important role in immune and inflammatory conditions. Substance P (SP), the unidecapeptide RPKPQQFFGLM-NH2, is known to upregulate the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α. We report here that 5 (Acetylamino) 4 oxo-6-phenyl-2-hexenoic acid methyl ester (AOPHA-Me) and 4 phenyl 3 butenoic acid (PBA), two anti-inflammatory compounds developed in our laboratory, reduce SP stimulated TNF-α expression in RAW 264.7 macrophages. We also show that AOPHA Me and PBA both inhibit SP stimulated phosphorylation of JNK and p38 MAPK. Furthermore, molecular modeling studies indicate that both AOPHA Me and PBA dock at the ATP binding site of apoptosis signal regulating kinase 1 (ASK1) with predicted docking energies of -7.0 kcal/mol and 5.9 kcal/mol, respectively; this binding overlaps with that of staurosporine, a known inhibitor of ASK1. Taken together, these findings support the conclusion that AOPHA Me and PBA inhibition of TNF-α expression in SP-stimulated RAW 264.7 macrophages is a consequence of the inhibition JNK and p38 MAPK phosphorylation. We have previously shown that AOPHA-Me and PBA inhibit the amidative bioactivation of SP, which also would be expected to decrease formation of pro-inflammatory cytokines. It is conceivable that this dual action of inhibiting amidation and MAPK phosphorylation may be of some advantage in enhancing the anti-inflammatory activity of a therapeutic molecule. We also encapsulated AOPHA-Me separately in polyketal and poly(lactic co glycolic acid) microparticles. The in-vitro release profiles of AOPHA-Me from these particles were characterized. We have also shown that AOPHA-Me, when encapsulated in PCADK microparticles, is an effective treatment for edema induced by adjuvant arthritis in rats. In separate work, it was determined that myo inositol 1,2,3,4,5,6 hexakisphosphate is an inhibitor to early-stage Loblolly pine somatic embryo growth. In addition, it was determined that muco inositol 1,2,3,4,5,6 hexakisphosphate is not an inhibitor to early-stage Loblolly pine somatic embryo growth. These experiments demonstrate the stereochemical dependence of myo inositol 1,2,3,4,5,6 hexakisphosphates inhibitory activity.

<p>Traditional small molecule chemotherapeutics show limited effectiveness in the clinic as their poor pharmacokinetics lead to rapid clearance from circulation and their exposure to off-target tissues results in dose-limiting toxicity. The objective of this dissertation is to exploit a class of recombinant chimeric polypeptides (CPs) to actively target drugs to tumors as conjugation to macromolecular carriers has demonstrated improved efficacy by increasing plasma retention time, reducing uptake by healthy tissues, and enhancing tumor accumulation by exploiting the leaky vasculature and impaired lymphatic drainage characteristic of solid tumors. CPs consist of two principal components: (1) a thermally responsive elastin-like polypeptide (ELP) that displays a soluble-to-aggregate phase transition above a characteristic transition temperature (Tt); and (2) a cysteine-rich peptide fused to one end of the ELP to which small molecule therapeutics can be covalently attached (the conjugation domain). This work describes the development of CP drug-loaded nanoparticles that can be targeted to solid tumors by the external application of mild regional hyperthermia (39-43°C). </p><p>Highly repetitive ELP polymers were assembled by Plasmid Reconstruction Recursive Directional Ligation (PRe-RDL), in which two halves of a parent plasmid, each containing a copy of an oligomer, were ligated together to dimerize the oligomer and reconstitute the functional plasmid. Chimeric polypeptides were constructed by fusing the ELP sequence to a (CGG)8 conjugation domain, expressed in Escherichia coli, and loaded with small molecule hydrophobes through site specific attachment to the conjugation domain. Drug attachment induced the assembly of nanoparticles that retained the thermal responsiveness of the parent ELP in that they experienced a phase transition from soluble nanoparticles to an aggregated phase above their Tt. Importantly, the Tt of these nanoparticles was near-independent of the CP concentration and the structure of the conjugated molecule as long as it displayed an octanol-water distribution coefficient (LogD) > 1.5. </p><p>A series of CP nanoparticles with varying ratios of alanine and valine in the guest residue position was used to develop a quantitative model that described the CP transition temperature in terms of three variables - sequence, chain length, and concentration - and the model was used to identify CPs of varying molecular weights that displayed transition temperatures between 39°C and 43°C. A murine dorsal skin fold window chamber model using a human tumor xenograft was used to validate that only the thermoresponsive CP nanoparticles (and not the controls) exhibited a micelle-to-aggregate phase transition between 39-43°C in vivo. Furthermore, quantitative analysis of the biodistribution profile demonstrated that accumulation of these thermoresponsive CP nanoparticles was significantly enhanced by applying heat in a cyclical manner. It is hoped that this work will provide a helpful resource for the use of thermoresponsive CP nanoparticles in a variety of biomedical applications.</p> / Dissertation

A new class of polymer coated lanthanide fluoride nanoparticle aggregates (NPAs) was developed as potential MRI contrast agents. The NPA synthesis has been perfected to control the size distribution and optimize relaxivities. Polyacrylic acid was used as a stabilizing polymer, and was conjugated to folic acid to improve targeting to SK-BR-3 breast cancer cells. Terbium was incorporated in the synthesis to study the passive and active targeting properties of NPAs. Through a series of microscopy experiments, a significant difference in uptake between NPAs with and without targeting moieties occurs after 48 hours of incubation. The relaxivity of the optimized nanoparticles was measured to be 56 s-1(mg/ml)-1 using a 1.5 T scanner, which may be compared to that of the commercially available Gd3+-DTPA [R1 = 7 s-1(mg/ml)-1]. Abdominal perfusion studies in rats also demonstrated that the NPAs provide better contrast of the vasculature than Gd3+-DTPA does at the same mass concentration.

The feasibility of highly dispersed gold nanocatalyst supported on yttria-stabilized zirconia (YSZ) for the model reactions of C2H4 and CO oxidation is demonstrated for the first time. Gold nanoparticles are synthesized on YSZ powder by chemical reduction of the precursor salt in the mixture of ethanol, water and polyvinylpyrrolidone (PVP). Resulting metal loading of the catalysts are 1 wt.% with average particle sizes ranging from 6 to 9 nm. Results of CO and C2H4 oxidation display catalytic activity at 65 0C and 25 0C for CO and C2H4 oxidation, respectively. The catalytic properties of the catalysts are different due to their average particle size. Electrochemical Promotion of Catalysis (EPOC) of C2H4 oxidation is demonstrated. Application of constant potential difference between two electrodes in the bipolar electrochemical cell led to increase in C2H4 conversion. A proposed mechanism explains the bipolar EPOC phenomenon through formation of O2- flux across the electrochemical cell, resulting in the change of Work Function of gold nanoparticles placed in between the electrodes and is electronically isolated.

Since the discovery of the high temperature superconductor YBa2Cu3O7-δ (YBCO), with transition temperature (Tc = 77 K), above liquid nitrogen point in 1987 many research projects have been dedicated to enhancing the high field performance of this material for practical applications. The 2nd generation YBCO-based coated conductors are believed to be the most promising approach for commercial applications including power transmission, motors, generators, and high field magnets. With the advances of nanotechnologies, different nanoengineering methods have been demonstrated to enhance the performance of YBCO thin films, include doping with 0-dimensional (0-D) self-assembled nanoparticles, 1-dimensional (1-D) nanorods, and 2-dimensional (2-D) nanolayers. Furthermore, dopants with ferromagnetic properties are also reported to provide enhanced pinning effects by Lorentz force, especially under high-applied magnetic fields. The principle of these methods is to generate high-density defects at the heterogeneous interfaces as artificial pinning centers in an effort to improve the flux-pinning properties. The morphology and dimensions of the nanoinclusions play an important role in pining enhancement. Optimized pinning structures are likely to be located at energetically favorable vortex cores, which form a triangular lattice with dimensions close to the YBCO coherence length ξ (ξab ~ 4 nm; ξc ~ 0.5 nm at 77 K.) However, it is challenging to achieve small dimensional nanodopants in the vapor deposited YBCO thin films. The purpose of this research is to utilize nanoengineering methods to produce optimized pinning structure in YBCO thin films. In this thesis, we systematically study the effects of different nanoinclusions on the flux-pinning properties of YBCO thin films. The 0-D ferromagnetic Fe2O3 and CoFe2O4 nanoparticles, 2-D CeO2 multilayers, and tunable vertically aligned nanocomposites (VAN) of (Fe2O3)x:(CeO2)1-x and (CoFe2O4)x:(CeO2)1-x systems are introduced into the YBCO matrix as artificial pinning centers. Results suggest that all nanoinclusions showed significant enhancement in the superconducting properties of YBCO. The ferromagnetic pinning centers dominate at high field and low temperature regimes, however, the defect pinning centers dominate at low field and high temperature regimes. The uniquely arranged VAN structure of alternating magnetic and non-magnetic nanophases, which incorporates both high defect density and tunable distribution of magnetic dopants, is believed to be an ideal solution for flux-pinning enhancement.