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- All Subjects: Nanoparticles
- Genre: Doctoral Dissertation
- Creators: Kodibagkar, Vikram
Description
Gold nanoparticles have emerged as promising nanomaterials for biosensing, imaging, photothermal treatment and therapeutic delivery for several diseases, including cancer. We have generated poly(amino ether)-functionalized gold nanorods (PAE-GNRs) using a layer-by-layer deposition approach. Sub-toxic concentrations of PAE-GNRs were employed to deliver plasmid DNA to prostate cancer cells in vitro. PAE-GNRs generated using 1,4C-1,4Bis, a cationic polymer from our laboratory demonstrated significantly higher transgene expression and exhibited lower cytotoxicities when compared to similar assemblies generated using 25 kDa poly(ethylene imine) (PEI25k-GNRs), a current standard for polymer-mediated gene delivery. Additionally, sub-toxic concentrations of 1,4C-1,4Bis-GNR nanoassemblies were employed to deliver expression vectors that express shRNA ('shRNA plasmid') against firefly luciferase gene in order to knock down expression of the protein constitutively expressed in prostate cancer cells. The roles of poly(amino ether) chemistry and zeta-potential in determining transgene expression efficacies of PAE-GNR assemblies were investigated. The theranostic potential of 1,4C-1,4Bis-GNR nanoassemblies was demonstrated using live cell two-photon induced luminescence bioimaging. The PAE class of polymers was also investigated for the one pot synthesis of both gold and silver nanoparticles using a small library poly(amino ethers) derived from linear-like polyamines. Efficient nanoparticle synthesis dependent on concentration of polymers as well as polymer chemical composition is demonstrated. Additionally, the application of poly(amino ether)-gold nanoparticles for transgene delivery is demonstrated in 22Rv1 and MB49 cancer cell lines. Base polymer, 1,4C-1,4Bis and 1,4C-1,4Bis templated and modified gold nanoparticles were compared for transgene delivery efficacies. Differences in morphology and physiochemical properties were investigated as they relate to differences in transgene delivery efficacy. There were found to be minimal differences suggestion that 1,4C-1,4Bis efficacy is not lost following use for nanoparticle modification. These results indicate that poly(amino ether)-gold nanoassemblies are a promising theranostic platform for delivery of therapeutic payloads capable of simultaneous gene silencing and bioimaging.
ContributorsRamos, James (Author) / Rege, Kaushal (Thesis advisor) / Kodibagkar, Vikram (Committee member) / Caplan, Michael (Committee member) / Vernon, Brent (Committee member) / Garcia, Antonio (Committee member) / Arizona State University (Publisher)
Created2014
Description
Dynamic susceptibility contrast MRI (DSC-MRI) is a powerful tool used to quantitatively measure parameters related to blood flow and volume in the brain. The technique is known as a “bolus-tracking” method and relies upon very fast scanning to accurately measure the flow of contrast agent into and out of a region of interest. The need for high temporal resolution to measure contrast agent dynamics limits the spatial coverage of perfusion parameter maps which limits the utility of DSC-perfusion studies in pathologies involving the entire brain. Typical clinical DSC-perfusion studies are capable of acquiring 10-15 slices, generally centered on a known lesion or pathology.
The methods developed in this work improve the spatial coverage of whole-brain DSC-MRI by combining a highly efficient 3D spiral k-space trajectory with Generalized Autocalibrating Partial Parallel Acquisition (GRAPPA) parallel imaging without increasing temporal resolution. The proposed method is capable of acquiring 30 slices with a temporal resolution of under 1 second, covering the entire cerebrum with isotropic spatial resolution of 3 mm. Additionally, the acquisition method allows for correction of T1-enhancing leakage effects by virtue of collecting two echoes, which confound DSC perfusion measurements. The proposed DSC-perfusion method results in high quality perfusion parameter maps across a larger volume than is currently available with current clinical standards, improving diagnostic utility of perfusion MRI methods, which ultimately improves patient care.
The methods developed in this work improve the spatial coverage of whole-brain DSC-MRI by combining a highly efficient 3D spiral k-space trajectory with Generalized Autocalibrating Partial Parallel Acquisition (GRAPPA) parallel imaging without increasing temporal resolution. The proposed method is capable of acquiring 30 slices with a temporal resolution of under 1 second, covering the entire cerebrum with isotropic spatial resolution of 3 mm. Additionally, the acquisition method allows for correction of T1-enhancing leakage effects by virtue of collecting two echoes, which confound DSC perfusion measurements. The proposed DSC-perfusion method results in high quality perfusion parameter maps across a larger volume than is currently available with current clinical standards, improving diagnostic utility of perfusion MRI methods, which ultimately improves patient care.
ContributorsTurley, Dallas C (Author) / Pipe, James G (Thesis advisor) / Kodibagkar, Vikram (Thesis advisor) / Frakes, David (Committee member) / Sadleir, Rosalind (Committee member) / Schmainda, Kathleen (Committee member) / Arizona State University (Publisher)
Created2017