Browsing by Subject "Near infrared"
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Item Controlled assembly of biodegradable gold nanoclusters for in vivo imaging(2015-12) Stover, Robert John; Johnston, Keith P., 1955-; Truskett, Thomas M; Fan, Donglei; Korgel, Brian; Sokolov, KonstantinGold nanoparticles are of interest in biomedical imaging applications due to their inert nature and ability to exhibit surface plasmon resonance. These phenomena can result in high near-infrared extinction (NIR) due to asymmetry or close interparticle spacings within gold structures, making these materials ideal for photoacoustic imaging. Using this imaging modality, these materials allow for high contrast compared to the body’s tissues which exhibit a transparent “window” between 700-1100 nm, making them perfect for early cancer detection. However many gold structures designed for this application fail to achieve high NIR-absorbance at the <5 nm sizes which are required for efficient kidney clearance. Therefore, we designed a system which assembles ~4 nm primary gold particles into closely-spaced clusters of controlled size using a biodegradable, weakly adsorbing polymer and balance of colloidal attractive and repulsive forces. Thus, when the polymer degrades in acidic environments – such as within cells – the residual charge on the primary particles leads to dissociation of the clusters back to renal-clearable constituents. Since proteins in the blood and cells can increase the diameter of the primary particles above the 5 nm threshold, nanoparticle surfaces were designed to have a mixture of charged and zwitterionic molecules to limit protein interactions through buried charges and increased particle hydration. Strongly-bound, zwitterionic thiol-containing ligands were also investigated to resist the intracellular exchange of biomolecules which could compromise the clearable nature of the particles. These decorated nanoparticles were then assembled into clusters through one of two methods which varied either gold and polymer concentrations through evaporation, or particle charge via electrolyte addition prior to quenching by dilution in DI water. Once assembled, clusters assembled with polymer showed dissociation behavior after incubation in pH 5 acidic solutions to mimic the cellular pH environment. In other cases, sintering of the gold nanoparticle clusters prevented such dissociation. This thesis demonstrates the ability to not only create biocompatible nanoparticle surfaces, but to establish control size control over nanocluster assemblies which are capable of being used as NIR contrast agents.Item Extension of tetrathiafulvalene conjugation through pyrrollic-based dyes : ExTTF porphyrin and ExTTF BODIPY(2013-12) Bill, Nathaniel Lloyd; Sessler, Jonathan L.The research and development of organic electron donors is essential in the discovery of photodynamic therapy photosensitizers and catalysts, as well as in the fabrication of organic-based electronic devices. Recently, [pi]-extended tetrathiafulvalenes (exTTFs) have emerged as important organic donors due to their superb electronic properties. However, in general, exTTFs lack significant absorption in the visible and near-infrared portions of the electromagnetic spectrum, thereby limiting their utility. This doctoral dissertation depicts the author's efforts to address this inherent drawback of exTTFs by extending the electronic conjugation of tetrathiafulvalene moieties through pyrrole-based chromophores. The reported findings describe the design, synthesis, properties and potential applications of exTTFs with greatly enhanced absorption profiles. The first Chapter provides a brief historical overview on the history and development of [pi]-extended tetrathiafulvalenes. The various conjugated linkers utilized in exTTF systems are reviewed. In the latter part of the Chapter, emphasis is given to the applications in which exTTFs find use. Chapter 2, as the major focus of the dissertation, details the synthesis and characteristics of a quinoidal porphyrin-bridged exTTF, termed MTTFP. Several metalated complexes, including the Zn, Co, Cu, and Ni derivatives of MTTFP are reported. Additionally, the electrochemical, photophysical, and structural properties of MTTFPs are discussed. We also detail our efforts to synthesize and characterize both the one- and two-electron oxidized forms of MTTFPs. Finally, we discuss our efforts to reversibly switch thermodynamic electron transfer from ZnTTFP to Li@C₆₀ through coordination of axial ligands. Chapter 3 describes the formation of a 2:1 supramolecular ionic porphyrin complex between the two-electron oxidized form of ZnTTFP and a tetranionic sulfonated porphyrin. The association constants and the X-ray crystal structure of the complex are reported. A brief discussion outlining the photophysical characteristics (performed in Prof. Shunichi Fukuzumi and Prof. Dongho Kim's group) of the porphyrin donor-acceptor complexes are included. Chapter 4 details the synthesis, photophysical properties, and spectroelectrochemistry of a difluoroboradiazaindacene (BODIPY) bridged exTTF. This compound is referred to as ex-BODIPY. A singlet oxygen generation study provides initial evidence that ex-BODIPY could potentially serve as a photosensitizer. All of the experimental procedures, characterization data, and X-ray crystallographic data tables are reported in Chapter 5.Item Textured thin metal shells on metal oxide nanoparticles with strong NIR absorbance and high magnetization for imaging and therapy(2010-12) Ma, Li, doctor of chemical engineering; Feldman, Marc David; Johnston, Keith P., 1955-; Milner, Thomas E.; Sokolov, Konstantin V.; Mullins, C. B.; Hwang, Gyeong S.The ability of sub 100 nm nanoparticles to target and modulate the biology of cells will enable major advancements in cellular imaging and therapy in cancer and atherosclerosis. A key challenge is to load an extremely high degree of targeting, imaging, and therapeutic functionality into small, yet stable particles. A general mechanism is presented for thin autocatalytic growth on nanoparticle substrates (TAGS), as demonstrated for a homologous series of < 5 nm textured Au coatings on < 42 nm iron oxide cluster cores. Very low Au supersaturation levels are utilized to prevent commonly encountered excessive autocatalytic growth that otherwise produce thick shells. The degree of separation of nucleation to form the seeds from growth is utilized to control the morphology and uniformity of the thin Au coatings. The thin and asymmetric Au shells produce strong near infrared (NIR) absorbance with a cross section of ~10⁻¹⁴ m², whereas the high magnetic content per particles provides strong r2 spin-spin magnetic relaxivity of 200 mM⁻¹s⁻¹. TAGS may be generalized to a wide variety of substrates and high energy coatings to form core-shell nanoparticles of interest in a variety of applications as diverse as catalysis and bionanotechnology. High uptake of the nanoclusters by macrophages is facilitated by the dextran coating, producing intense NIR contrast both in cell culture and an in vivo rabbit model of atherosclerosis. A novel conjugation technique further allows covalent binding of anti-epidermal growth factor receptor (EGFR) monoclonal antibody (Ab) to the nanoclusters for highly selective targeting to EGFR over expressing cancer cells. AlexaFluor 488 tagged Ab nanocluster conjugates were prepared to correlate the number of conjugated Abs with the hydrodynamic diameter. The high targeting efficacy was evaluated by dark field reflectance imaging and atomic absorbance spectrometry (AAS). Colocalization of the nanoparticles by dual mode in-vitro imaging with dark field and fluorescence microscopy demonstrates the Abs remained attached to the Au surfaces. The extremely high curvature of the Au shells with features below 5 nm influence the spacing and orientations of the Abs on the surface, which has the potential to have a marked effect on biological pathways within cells. These targeted small multifunctional nanoclusters may solve some key molecular imaging challenges for cancer and atherosclerosis.