Browsing by Subject "Gold nanorod"
Now showing 1 - 3 of 3
Results Per Page
Sort Options
Item Intravascular photoacoustics as a theranostic platform for atherosclerosis(2014-08) Yeager, Douglas Edward; Emelianov, Stanislav Y.; Baker, Aaron; Sessler, Jonathan; Smalling, Richard; Sokolov, KonstantinThe persistence of high global mortality rates directly attributable to cardiovascular disease drives ongoing research into novel approaches for improved diagnosis and treatment of its primary underlying cause, atherosclerosis. Combined intravascular ultrasound and photoacoustic (IVUS/IVPA) imaging is one such modality, actively being developed as a tool for improved characterization of high-risk atherosclerotic plaques. The pathophysiology associated with progression and destabilization of atherosclerotic plaques leads to characteristic changes in arterial morphology and composition. IVUS/IVPA imaging seeks to expand upon the ability of clinically utilized intravascular ultrasound (IVUS) imaging to assess vessel anatomy by adding improved sensitivity to image the underlying cellular and molecular composition through intravascular photoacoustic (IVPA) imaging of either endogenous chromophores (e.g. lipid) or exogenously delivered contrast agents. This dissertation focuses on the expansion of IVUS/IVPA imaging using exogenous contrast agents to enable the detection and subsequent optically-triggered therapy of atherosclerotic plaques. The passive extravasation and aggregation of systemically injected plasmonic gold nanorods absorbing within the near infrared tissue optical window within plaques of atherosclerotic rabbit models is first demonstrated, along with the ability to localize the contrast agents using ex vivo IVUS/IVPA imaging. The motivation for nanoparticle labeling of atherosclerosis is then expanded from that of purely image contrast agents to vehicles for image-guided, dual-modality phototherapy. The integrated IVUS/IVPA imaging catheter is utilized for photothermal delivery with simultaneous IVPA temperature monitoring using the high optical absorption of gold nanorod contrast agents to enable localized heating. Subsequently, the potential role for IVUS/IVPA-guided phototherapy is further expanded through the characterization and in vitro assessment of novel multifunctional theranostic nanoparticles comprised of a gold nanorod core with a degradable, photosensitizer-doped silica shell. Together, the results presented within this dissertation provide a framework for ongoing research into the expansion of IVUS/IVPA imaging as a platform for complimentary diagnosis and local treatment of atherosclerotic plaques using multifunctional theranostic nanoparticle contrast agents.Item Investigation of gold nanoparticle accumulation kinetics for effective cancer targeting(2010-08) Park, Jaesook; Tunnell, James W.; Dunn, Andrew K.; Sokolov, Konstantin; Roy, Krishnendu; Krishnan, SunilGold nanoparticles (GNP) have been widely used as optical imaging and photothermal therapy agents due to their biocompatibility, simplicity of conjugation chemistry, optical tunability and efficient light conversion to heat. A number of in vitro and in vivo studies have demonstrated that they can be used as effective thermal therapy and imaging contrast agents to treat and diagnose cancer. As clinical applications of GNPs for cancer imaging and therapy have gained interest, efforts for understanding their accumulation kinetics has become more important. Given the recent demonstration of intrinsic two-photon induced photoluminescence (TPIP) of gold nanoshells (GNSs) and gold nanorods (GNRs), TPIP imaging is an efficient tool for investigating the microscopic distribution of the GNPs at intra-organ level. The following work explores these GNPs’ physical and optical properties for effective use of GNPs in TPIP imaging and examines the feasibility of using intrinsic TPIP imaging to investigate GNP’s biodistribution in bulk tumors and thin tissue slices processed for standard histology. Our results showed that GNPs yield a strong TPIP signal, and we found that the direct luminescence-based contrast imaging of GNPs can image both GNPs and nuclei, cytoplasm or vasculature simultaneously. Also, we present the effect of GNP morphology on their distribution within organs. Collected images showed that GNPs had a heterogeneous distribution with higher accumulation at the tumor periphery. However, GNRs had deeper penetration into tumor than GNRs due to their shape and size. In addition, GNPs were observed in unique patterns close to vasculature. Finally, we introduce single- and multiple-dose administrations of GNPs as a way of increasing GNP accumulation in tumor. Our results show that multiple dosing can increase GNP accumulation in tumor 1.6 to 2 times more than single dosing. Histological analysis also demonstrated that there were no signs of acute toxicity in tumor, liver and spleen excised from the mice receiving 1 injection, 5 injections of GNPs and trehalose injection.Item Sub-diffraction limited imaging of plasmonic nanostructures(2014-08) Titus, Eric James; Willets, Katherine A.This thesis is focused on understanding the interactions between molecules and surface-enhanced Raman scattering (SERS) substrates that are typically unresolved due to the diffraction limit of light. Towards this end, we have developed and tested several different sub-diffraction-limited imaging techniques in order to observe these interactions. First, we utilize an isotope-edited bianalyte approach combined with super-resolution imaging via Gaussian point-spread function fitting to elucidate the role of Raman reporter molecules on the location of the SERS emission centroids. By using low concentrations of two different analyte molecules, we find that the location of the SERS emission centroid depends on the number and positions of the molecules present on the SERS substrate. It is also known that SERS enhancement partially results from the molecule coupling its emission into the far-field through the plasmonic nanostructure. This results in a particle-dictated, dipole-like emission pattern, which cannot be accurately modeled as a Gaussian, so we tested the applicability of super-resolution imaging using a dipole-emission fitting model to this data. To test this model, we first fit gold nanorod (AuNR) luminescence images, as AuNR luminescence is primarily coupled out through the longitudinal dipole plasmon mode. This study showed that a three-dimensional dipole model is necessary to fit the AuNR emission, with the model providing accurate orientation and emission wavelength parameters for the nanostructure, as confirmed using correlated AFM and spectroscopy. The dipole fitting technique was next applied to single- and multiple-molecule SERS emission from silver nanoparticle dimers. We again found that a three-dimensional dipole PSF was necessary to accurately model the emission and orientation parameters of the dimer, but that at the single molecule level, the movement of the molecule causes increased uncertainty in the orientation parameters determined by the fit. Finally, we describe progress towards using a combined atomic force/optical microscope system in order to position a carbon nanotube analyte at known locations on the nanoparticle substrate. This would allow for the simultaneous mapping of nanoparticle topography and exact locations of plasmonic enhancement around the nanostructure, but consistently low signal-to-noise kept this technique from being viable.