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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

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
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Description
Proton beam therapy (PBT) is a state-of-the-art radiotherapy treatment approach that uses focused proton beams for tumor ablation. A key advantage of this approach over conventional photon radiotherapy (XRT) is the unique dose deposition characteristics of protons, resulting in superior healthy tissue sparing. This results in fewer unwanted side effects

Proton beam therapy (PBT) is a state-of-the-art radiotherapy treatment approach that uses focused proton beams for tumor ablation. A key advantage of this approach over conventional photon radiotherapy (XRT) is the unique dose deposition characteristics of protons, resulting in superior healthy tissue sparing. This results in fewer unwanted side effects and improved outcomes for patients. Current available dosimeters are intrinsic, complex and expensive; hence cannot be used to determine the dose delivered to the tumor routinely. Here, we report a hydrogel based plasmonic nanosensor for measurements of clinical doses in ranges between 2-4 GyRBE. In this nanosensor, gold ions, encapsulated in a hydrogel, are reduced to gold nanoparticles following irradiation with proton beams. Formation of gold nanoparticles renders a color change to the originally colorless hydrogel. The intensity of the color can be used to calibrate the hydrogel nanosensor in order to quantify different radiation doses employed during treatment. The potential of this nanosensor for clinical translation was demonstrated using an anthropomorphic phantom mimicking a clinical radiotherapy session. The simplicity of fabrication, detection range in the fractionated radiotherapy regime and ease of detection with translational potential makes this a first-in-kind plasmonic colorimetric nanosensor for applications in clinical proton beam therapy.
ContributorsInamdar, Sahil (Author) / Rege, Kaushal (Thesis advisor) / Anand, Aman (Committee member) / Nannenga, Brent (Committee member) / Arizona State University (Publisher)
Created2017
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Description
This research addresses the need for improvement in radiation sensors for applications of ionizing radiation such as radiotherapy. The current sensors involved are polymer gel dosimeters, MOSFETs, radio-chromic films, etc. Most of the sensors involved require expensive equipment's and processing facilities for readout. There is still a need to develo

This research addresses the need for improvement in radiation sensors for applications of ionizing radiation such as radiotherapy. The current sensors involved are polymer gel dosimeters, MOSFETs, radio-chromic films, etc. Most of the sensors involved require expensive equipment's and processing facilities for readout. There is still a need to develop better sensors that can be clinically applied. There are numerous groups around the world trying to conceive a better dosimeter. One of the radiation sensors that was developed recently was based on fluorescence signal emitted from the sensor. To advance the field of radiation sensors, a visual indicator has been developed in-lab as a method of detect ionizing radiation. The intensity of change in color is directly dependent on the amount of incident ionizing radiation. An aqueous gold nanoparticle sensor can be used to accurately determine the incident amount of ionizing radiation1. A gold nanoparticle sensor has been developed in lab with the use of hexadecyltrimethylammonium bromide (C16TAB) as the templating molecule. In the presence of ionizing radiation, the colorless gold salt is reduced and templated, creating a dispersion within the fluid1. The formation of suspended nanoparticles leads to a color change that can be visually detected and accurately analyzed through the employment of a spectrometer. Unfortunately, the toxicity of C16TAB is high. It is expected the toxicity can be reduced by replacing C16TAB with an amino acid, as amino acids can act as templating molecules in the solution and many are naturally occuring2. The experiments included a screening of 20 natural amino acids and 12 unnatural amino acids with the gold salt solution in the presence of ionizing radiation. Stability and absorbance testing was conducted on the amino acid sensors. Additional screening of lead amino acid sensors at various concentrations of irradiation was conducted.
ContributorsGupta, Saumya (Co-author) / Rege, Kaushal (Co-author, Thesis director) / Pushpavanam, Karthik (Co-author, Committee member) / Chemical Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05