The strong electromagnetic field that is induced at the surface of a plasmonic nanoparticle can be utilized for many important applications, including spectroscopic enhancement and electromagnetic waveguides. The focus of this thesis is to study some of the properties of induced plasmonic fields around metal nanoparticles. Current methodologies for fabricating nanoparticles are discussed, including lithography and colloidal synthesis. This dissertation includes studies on plasmonic driven nanoparticle motion of surface supported gold nanoprisms from a substrate into solution via a femtosecond pulse. The mechanism of particle motion is discussed and the stability of the unprotected nanoprisms in solution is studied. Fundamental plasmonic near-field coupling between two plasmonic nanoparticles is also examined. Experimental results using electron beam lithography fabricated samples are used to explicitly describe the plasmonic coupling between dimers as a function of the nanoparticle size, shape, and orientation. These variables are systematically studied and the dependence is compared to mathematically derived functional dependencies in order to model and predict the effects of plasmonic coupling. As an extension, the coupling between plasmonic nanoparticles is shown in a common application, surface enhanced Raman scattering. The final chapter is devoted to an investigation of the nature of nanocatalysis, homogeneous and heterogeneous, for several reactions using metal nanoparticles.

The work presented in this thesis shows how tunneling spectroscopy techniques can be applied to metallic nanoparticles to obtain useful information about fundamental physical processes in nanoscopic length scales. At low temperatures, the discrete character of the energy spectrum of these particles, allows the study of spin-polarized current via resolved "electron-in-a-box" energy levels. In samples consisting of two ferromagnetic electrodes tunnel coupled to single aluminum nanoparticles, spin accumulation mechanisms are responsible for the observed spin-polarized current. The observed effect of an applied perpendicular magnetic field, relative to the magnetization orientation of the electrodes, indicates the suppression of spin precession in such small particles. More generally, in the presence of an external non-collinear magnetic field, it is the local field "felt" by the particle that determines the character of the tunnel current. This effect is also observed in the case where only one of the electrodes is ferromagnetic. In contrast to the non-magnetic case, ferromagnetic nanoparticles exhibit a much more complex energy spectrum, which cannot be accounted for, using the simple free-electron picture. It will be shown that interactions between quasi-particle excitations due to sequential electron tunneling and spin excitations in the particle are likely to play an important role in the observed temperature/voltage dependence of magnetic hysteresis loops.

Molecular optical imaging enables the ability to non-invasively image biological function. When used in conjunction with optical contrast agents, molecular imaging can provide biomarker-specific information with subcellular spatial resolution. Plasmonic nanoparticles are unique optical contrast agents due to the fact that the intensity and peak wavelength of scattering is dependant on interparticle spacing. This distance dependance puts these nanosensors in a position to probe molecular interactions by exploiting contrast between isolated and closely spaced nanoparticles. This dissertation presents the first intracellular molecular imaging platform using multifunctional gold nanoparticles which incorporate both cytosolic delivery and targeting moieties on the same particle. In order to produce robust nanosensors, a novel conjugation strategy was developed involving a heterofunctional linker capable of rigidly attaching various components to the nanoparticle surface. Since most biomarkers of interest are localized intracellularly, the delivery functionality was a key focus. It was achieved using the TAT-HA2 fusion peptide which has been previously shown to enhance both endosomal uptake and subsequent release into the cytosol. The feasibility of these nanoparticles as intracellular sensors was proposed by attempting to image actin rearrangement in live fibroblasts. The assembly of nanoparticles at the leading of motile cells was which was potentially due to actin targeting resulted in a red shift in scattering maxima due to plasmon resonance coupling between particles as well as a dramatic increase in scattering intensity. Although several challenges still exist, the potential for these contrast agents as nanosensors for the presence of proteins implicated in viral carcinogenesis is also introduced. / text

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

Current methods to diagnose and treat cancer often involve expensive, time-consuming equipment and materials that may lead to unwanted side effects and may not even increase a patient’s chance of survival. Thus, for a while now, a large part of the research community has focused on developing improved methods to detect, diagnose, and treat cancer on the molecular scale. One of the most recently discovered methods of cancer therapy is targeted therapy. These targeted therapies have potential to provide a patient with a form of personalized medicine because these therapies are biological molecules that specifically target other molecules involved with a cancer’s growth. Past trials using these therapeutic molecules, however, have led to controversial results, where certain patients responded better than others to the therapy for unknown reasons. Elucidating the reason behind these mixed results can be accomplished using metal nanoparticle technologies which could provide a bright signal to monitor the path that these therapeutic molecules take in vivo as well as enhance the molecule’s efficacy. Literature has shown that presenting targeting molecules in a dense manner to their target will increase these molecules’ binding affinity. This concept has been explored here to increase binding affinity of therapeutic molecules by attaching these molecules in a dense manner on the surface of gold nanoparticles, and correlating this increased affinity with therapeutic efficacy. Additionally, gold nanoparticles provide an easy surface for molecules to be functionalized on and have shown to be effective imaging, x-ray, and photothermal therapy agents. A major roadblock to using these gold nanoparticles clinically is their non-degradability and thus potential to cause long-term negative side effects in vivo. A platform for developing biodegradable gold nanoparticles is also explored here to take advantage of the gold nanoparticles’ excellent imaging and drug delivery capabilities while still allowing them to be used safely in the long term. / text

The advance of nanotechnology has made it possible that pure silver can be engineered into nano scale level with less than 100 nm in size. So far many studies have confirmed anti-bacterial and anti-inflammatory efficacy of silver nanoparticles (AgNPs). In our previous study we have revealed that AgNPs could promote wound healing through modulation of cytokines in a burn wound model in mice. Nonetheless, the exact effects mediated by AgNPs on various cell types in skin, including keratinocytes and fibroblasts, during wound healing still remain unknown. Therefore, in the present study we targeted a full-thickness excisional wound model in mice to explore the action and potential toxicity of AgNPs on keratinocytes and fibroblasts. Immunohistochemistry staining and molecular assay were conducted to explore AgNPs-induced re-epithelization and cell differentiation in both in vivo and in vitro studies. We next targeted the healed skin after AgNPs-mediated wound healing using tensile test to compare their mechanical function. Meanwhile, immunohistochemistry staining and quantitative assay were utilized to further investigate and compare collagen deposition, and scanning electron microscopy (SEM) was used to observe the morphology and distribution of collagen fibrils in healed skin. Moreover, AgNPs of different sizes and doses were studied to investigate the potential toxicity, their influence on cell migration, and extracellular matrix (ECM) production. Key results: 1. AgNPs could accelerate excisional wound healing in mouse skin when compared with other formats of silver. 2. AgNPs mediated differential cellular response in skin cells. They promoted proliferation and migration of keratinocytes in epidermal layer, through which the re-epithelization process during wound healing was enhanced; while proliferation of fibroblasts in dermal layer was inhibited and they were driven into the differentiation of myofibroblasts, through which wound contraction process was strengthened. 3. AgNPs could suppress the proliferation of human keloid fibroblasts and ECM production including collagen, fibronectin and heat shock protein, which would suggest that AgNPs had anti-fibrosis effect. 4. The AgNPs could stimulate the proliferation of epidermal progenitors and their differentiation into keratinocytes during wound healing. This biological event further contributed to the re-epithelization process. 5. AgNPs-mediated healed skin possessed comparable mechanical function, collagen deposition and fibril alignment to normal skin, which suggested AgNPs could modulate collagen production during skin wound healing. 6. The inhibitory effect on fibroblasts and cytotoxicity mediated by AgNPs showed a dose-dependent and size-dependent manner. In conclusion, AgNPs not only contribute to healing of infected skin wounds through antibacterial activity, but can also accelerate wound healing through mediating differential cellular responses in different skin cell types and modulate collagen production during wound healing. Furthermore, there should be an optimal concentration and size to exert maximal biological action with minimal toxicity for each specific cell type. Present studies further extended our knowledge of AgNPs and have implications for treatment of wounds in clinical setting. / published_or_final_version / Surgery / Doctoral / Doctor of Philosophy

Gold nanoparticles attain an intense focus in biomedical imaging applications due to their unique optical properties, facile conjugation with biomolecules, and biocompatibility. Although a considerable amount of work towards the development of gold nanoparticles has been completed, these promising contrast agents have not yet reached the clinic due to several challenges including efficient accumulation at the diseased site, sensitivity of detection in vivo, potential adverse effects, and clearance from the body. High signal-to-background ratio is required to enhance sensitivity of detection. Because near infrared (near-IR) light has the best tissue penetration, contrast agents designed to work in this range can significantly increase imaging sensitivity. Moreover, efficient targeting of the molecular biomarkers on diseased cells can decrease the required dosage, increase the site-specific accumulation, and enhance the imaging sensitivity. Molecular-specific contrast agents developed in this project use directional attachment of antibody molecules to the nanoparticle surface, enhancing the targeting efficacy. Additionally, cell-based delivery of diagnostic and therapeutic agents is gaining much interest due to the immune cells’ special access to the avascular, diseased regions. The contrast agents developed in this project enable detection of just a few cells per unit of imaging volume, enable multiplex imaging, and open up a possibility for tracking different cell populations with noninvasive photoacoustic and ultrasound imaging. Finally, the clearance of nanoparticles from the body dictates their clinical translation. The in vivo pharmacokinetics study along with the proposed in vitro model explored in this project will enable fast, reliable, and cost-efficient screening of promising agents and facilitate quick optimization of nanoparticles for their potential use in the clinic. / text

Imaging of biomolecules on the nano-scale is a crucial developing technology with major implications for our understanding of biological systems and for detection and therapy of disease. Plasmonic nanoparticles are a key optical contrast agent whose signal is generated by the collective oscillation of electrons in the metal particle. The resonance behavior of the electrons depends strongly on the arrangement of neighboring nanoparticles in a structure. This property may be exploited in imaging applications to report information on nanoscale morphology of targeted biomolecules. While the effect of plasmon resonance coupling has been studied in dimers and linear arrays of nanoparticles, this phenomenon remains largely unexplored in the case of 2D and 3D assemblies which are important in molecular cell imaging. This dissertation demonstrates how the optical signal from assemblies of gold nanoparticles can be related to nanoscale morphology in cellular imaging systems. First, the scattering spectra from live cells labeled with gold nanoparticles were collected and compared to the nanoscale arrangement of the particles in the same cells as determined by electron micrograph. Then, trends in scattering spectra with respect to nanoparticle arrangement were analyzed using a model system that allowed precise control over arrangement of nanoparticles. Several approaches to creating these model systems are discussed including biochemical linking, capillary assembly of colloidal particles, and direct deposition of gold onto substrates patterned by electron beam lithography. Spectral properties of the assemblies including peak position, width, and intensity are gathered and related to model variables including interparticle gap and overall particle number. It is shown that the redshift in the scattering spectra from nanoparticle assemblies is derived from both the particle number and the gap and is due to near-field coupling of particles as well as phase retardation of the scattered wave. The redshift behavior saturates as the number of particles in the aggregate increases but the saturation point depends strongly on interparticle gap. The drastic dependence of the red-shift saturation on the gap between nanoparticles has not been previously described; this phenomenon can have significant impact on the development of nanoparticle contrast agents and plasmonic sensor arrays. / text

This dissertation describes a novel methodology to prepare, functionalize, and assemble polymer-coated ferromagnetic cobalt nanoparticles (PS-CoNPs) and cobalt oxide nanowires. This research demonstrated the ability to use dipolar nanoparticles as `colloidal monomers' to form electroactive 1-D mesostructures via self- and field-induced assembly. The central focus of this dissertation is in developing a novel methodology termed as `Colloidal Polymerization', in the synthesis of well-defined cobalt oxide nanowires as nanostructured electrode materials for potential applications in energy storage and conversion.Ferromagnetic nanoparticles are versatile building blocks due to their inherent spin dipole, which drive 1-D self-assembly of colloids. However, the preparation and utilization of ferromagnetic nanoparticles have not been extensively examined due to the synthetic challenges in preparing well-defined materials that can be easily handled. This dissertation has overcome these challenges through the hybridization of polymeric surfactants with an inorganic colloid to impart functionality, colloidal stability and improved processing characteristics. This modular synthetic approach was further simplified to prepare ferromagnetic nanoparticles in gram scale, which enabled further investigations to develop new chemistry and materials science with these materials. These polymer-coated magnetic nanoparticles self-assembled into extended linear chains due to strong dipolar attractions between colloids. Additionally, novel dipolar assemblies, such as, flux-closure nanorings and lamellae type mesostructures were demonstrated by controlling the interparticle of attractive forces (dipolar versus van der Waals).The research presented herein focused on utilizing polymer-coated ferromagnetic cobalt nanoparticles as `colloidal molecules' to form interconnected 1-D mesostructures via `Colloidal Polymerization'. This process exploited the magnetic organization of dipolar colloids into 1-D mesostructures followed by a facile oxidation reaction to form interconnected electroactive cobalt oxide nanowires. This facile and template free approach enabled the large scale synthesis of semiconductor cobalt oxide nanowires, in which the electronic and electrochemical properties were confirmed for potential applications for energy storage and conversion. This work served as a platform in fabricating a wide range of semiconductor heterostructures, which allowed for structure-property investigation of new nanostructured electrodes.

Liquid crystals (LCs) are an interesting class of materials that are attracting significant attention due to their ever-growing applications in a wide variety of fields such as liquid crystal display (LCD) technology, materials science and bioscience. In recent years, along with the developments of materials at the nanoscale, doping LCs with nanoparticles (NPs) has emerged as a very promising approach for improving LC properties. Nanoparticle additives can introduce novel effects on optical and electro-optical properties of nematic liquid crystals (N-LCs), such as altered molecular alignment, faster response time and increased efficiency. This thesis studies the impacts that the inclusion of metallic NPs made of gold or semiconductor CdSe quantum dots (QDs), have on optical and electro-optical properties of N-LCs. Using polarized optical microscopy and detailed capacitance and transmittance measurements of nematic mixtures in electro-optic test cells, characteristics such as optical texture, phase transition temperatures, switching voltages and dielectric anisotropy are investigated in pure as well as doped samples. Surface ligands in NPs and their chemical functionalization play an important role in the LC-NP interactions, largely by determining the dispersibility of NPs and stability of the nanocomposites. One important objective of this thesis is to investigate and prepare a series of gold nanoparticles (Au NPs) with specially formulated robust coatings that maximizes solubility and stability in LC medium. Silanization of NPs is developed as a method to overcome the stability challenge. The functionalization of silanized NPs with aliphatic ligands or liquid crystalline molecules, provides chemically and thermally stable NPs with hydrophobic and structurally compatible surfaces required for dispersion in N-LCs. After complete characterization the synthesized particles are used to make the new nematic nanocomposites. By analysis of the structure-property relationships governing LC-nanomaterial composites and by comparison of new results and data from previous studies on other types of NPs, this thesis will further reveal the mechanism of the interrelations between host LC molecules and NP, considering the role of variables such as core composition, size and surface chemistry of NPs (e.g. siloxane shell, aliphatic ligand vs. liquid crystalline ligand) in achieving stable LC composites with desired optical and electro-optical properties.