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This dissertation provides a fundamental understanding of the impact of bulk polymer properties on the nanometer length scale modulus. The elastic modulus of amorphous organic thin films is examined using a surface wrinkling technique. Potential correlations between thin film behavior and intrinsic properties such as flexibility and chain length are

This dissertation provides a fundamental understanding of the impact of bulk polymer properties on the nanometer length scale modulus. The elastic modulus of amorphous organic thin films is examined using a surface wrinkling technique. Potential correlations between thin film behavior and intrinsic properties such as flexibility and chain length are explored. Thermal properties, glass transition temperature (Tg) and the coefficient of thermal expansion, are examined along with the moduli of these thin films. It is found that the nanometer length scale behavior of flexible polymers correlates to its bulk Tg and not the polymers intrinsic size. It is also found that decreases in the modulus of ultrathin flexible films is not correlated with the observed Tg decrease in films of the same thickness. Techniques to circumvent reductions from bulk modulus were also demonstrated. However, as chain flexibility is reduced the modulus becomes thickness independent down to 10 nm. Similarly for this series minor reductions in Tg were obtained. To further understand the impact of the intrinsic size and processing conditions; this wrinkling instability was also utilized to determine the modulus of small organic electronic materials at various deposition conditions. Lastly, this wrinkling instability is exploited for development of poly furfuryl alcohol wrinkles. A two-step wrinkling process is developed via an acid catalyzed polymerization of a drop cast solution of furfuryl alcohol and photo acid generator. The ability to control the surface topology and tune the wrinkle wavelength with processing parameters such as substrate temperature and photo acid generator concentration is also demonstrated. Well-ordered linear, circular, and curvilinear patterns are also obtained by selective ultraviolet exposure and polymerization of the furfuryl alcohol film. As a carbon precursor a thorough understanding of this wrinkling instability can have applications in a wide variety of technologies.
ContributorsTorres, Jessica (Author) / Vogt, Bryan D (Thesis advisor) / Stafford, Christopher M (Committee member) / Richert, Ranko (Committee member) / Rege, Kaushal (Committee member) / Dai, Lenore (Committee member) / Arizona State University (Publisher)
Created2011
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Description
Cancer diseases are among the leading cause of death in the United States. Advanced cancer diseases are characterized by genetic defects resulting in uncontrollable cell growth. Currently, chemotherapeutics are one of the mainstream treatments administered to cancer patients but are less effective if administered in the later stages of

Cancer diseases are among the leading cause of death in the United States. Advanced cancer diseases are characterized by genetic defects resulting in uncontrollable cell growth. Currently, chemotherapeutics are one of the mainstream treatments administered to cancer patients but are less effective if administered in the later stages of metastasis, and can result in unwanted side effects and broad toxicities. Therefore, current efforts have explored gene therapy as an alternative strategy to correct the genetic defects associated with cancer diseases, by administering genes which encode for proteins that result in cell death. While the use of viral vectors shows high level expression of the delivered transgene, the potential for insertion mutagenesis and activation of immune responses raise concern in clinical applications. Non-viral vectors, including cationic lipids and polymers, have been explored as potentially safer alternatives to viral delivery systems. These systems are advantageous for transgene delivery due to ease of synthesis, scale up, versatility, and in some cases due to their biodegradability and biocompatibility. However, low efficacies for transgene expression and high cytotoxicities limit the practical use of these polymers. In this work, a small library of twenty-one cationic polymers was synthesized following a ring opening polymerization of diglycidyl ethers (epoxides) by polyamines. The polymers were screened in parallel and transfection efficacies of individual polymers were compared to those of polyethylenimine (PEI), a current standard for polymer-mediated transgene delivery. Seven lead polymers that demonstrated higher transgene expression efficacies than PEI in pancreatic and prostate cancer cells lines were identified from the screening. A second related effort involved the generation of polymer-antibody conjugates in order to facilitate targeting of delivered plasmid DNA selectively to cancer cells. Future work with the novel lead polymers and polymer-antibody conjugates developed in this research will involve an investigation into the delivery of transgenes encoding for apoptosis-inducing proteins both in vitro and in vivo.
ContributorsVu, Lucas (Author) / Rege, Kaushal (Thesis advisor) / Nielsen, David (Committee member) / Sierks, Michael (Committee member) / Arizona State University (Publisher)
Created2011
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Description
Increased investigation into the development of macromolecular fluorophores has resulted in the synthesis and discovery of several potential candidates. These include modified and polymeric based dendritic structures, hyperbranched polymers and linear polymers. Strong inherent blue photoluminescence has been recently described in linear polyamine polymers in the absence of any chemical

Increased investigation into the development of macromolecular fluorophores has resulted in the synthesis and discovery of several potential candidates. These include modified and polymeric based dendritic structures, hyperbranched polymers and linear polymers. Strong inherent blue photoluminescence has been recently described in linear polyamine polymers in the absence of any chemical modifications. Here we describe the screening of amine/polyamine compounds for inherent photoluminescence. Several compounds that exhibited strong inherent blue photoluminescence following excitation with UV light were identified. Furthermore we demonstrated successful synthesis of poly(amino ether) polymers as well as chemically cross-linked poly(amino ether) thermosets with the lead Pentaethylenehexamine which was found to have strong inherent blue photoluminescence. The polymers and thermosets were found to retain the photoluminescent properties of the original lead compound. The polymers and thermosets were investigated for their ability to sequester heavy metals from aqueous solutions. An increased decrease in initial photoluminescence was observed as the materials were incubated with increasing metal salt concentration as a result of metal binding sequestration. The poly(amino ether) polymers were found to have higher sensitivity for metal sequestration when compared to equivalent amount of linear 25 kDa polyethylenimine. The strong inherent blue photoluminescence and the ease of synthesis of the poly(amino ether) polymers and thermosets give these materials strong potential for future applications as sensors.
ContributorsVu, Jeffrey (Co-author) / Ramos, James (Co-author) / Rege, Kaushal (Thesis director) / Godeshala, Sudakhar (Committee member) / Barrett, The Honors College (Contributor) / Chemical Engineering Program (Contributor)
Created2015-05
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Description
Current wound closure technology is limited, and lacks key elements \u2014 such as the formation of an immediate seal \u2014 that could otherwise resolve some of the common and life threatening complications associated with certain surgeries. Previous research has produced nanosealants capable of providing that immediate seal through the use

Current wound closure technology is limited, and lacks key elements \u2014 such as the formation of an immediate seal \u2014 that could otherwise resolve some of the common and life threatening complications associated with certain surgeries. Previous research has produced nanosealants capable of providing that immediate seal through the use of laser activation with a near infrared laser. Here, we have developed a biocompatible suture utilizes the same mechanics to provide the tensile strength needed to replace or supplement existing suture lines. Laser activated tissue integrating sutures (LATIS), are shown to have 75% of the tensile strength of commercially available PGA sutures, while still exhibiting the same laser mediated localized heating effect at power densities of as low as 1.6 W/cm2. LATIS has been shown to reach the temperature ranges needed for protein interdigitation, but suffers from low wet mechanical strength. Preparatory steps or solvents for chemical crosslinking generally dehydrate LATIS sutures, causing a shriveling effect that weakens the overall mechanical strength of the suture. To resolve this, a new method of drying, by which LATIS sutures are dried under tension on a suspended platform, has been shown to decrease control suture strength, but restore the strength of chemically treated LATIS sutures to the level of control sutures or above. These promising results suggest that follow-up work with chemical cross-linkers may produce the increases in LATIS wet strength that are needed for its implementation in deeper tissue surgeries.
ContributorsChang, Andy (Author) / Rege, Kaushal (Thesis director) / Goklany, Sheba (Committee member) / School of Molecular Sciences (Contributor) / Chemical Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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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
Description

Aminoglycosides contain a basic unit of an amino-modified glycoside (sugar) and have potent antibacterial properties used to treat a wide range of bacterial infections, including those that occur in the soft tissue, chest, urinary tract, and endocardial tissue.1, 2 With a broad spectrum of activity and convenient dosing schedule, Aminoglycoside

Aminoglycosides contain a basic unit of an amino-modified glycoside (sugar) and have potent antibacterial properties used to treat a wide range of bacterial infections, including those that occur in the soft tissue, chest, urinary tract, and endocardial tissue.1, 2 With a broad spectrum of activity and convenient dosing schedule, Aminoglycoside helps to effectively fight off Gram-negative bacteria.1, 3 In 1944 an aminoglycoside called streptomycin entered clinical trials to test its effectiveness as an antibiotic.4 After several years other classes of aminoglycosides were discovered such as neomycin, gentamicin, kanamycin, and netilmicin.4 When introduced these antibiotics presented major clinical advancements in the treatment of Tuberculosis and other bacterial infections.3, 4 However their use in modern medicine has diminished due to their toxicity, required parenteral delivery, and the availability of alternative antibiotics.3, 5 The dose-dependent toxicity of aminoglycosides limits their use due to a narrow range of safe aminoglycoside plasma concentrations.3, 5 Exceeding this range in non-target tissues can lead to negative effects on the audio-vestibular apparatus and kidneys.3, 5, 6 In the 1980’s, clinicians began treating infections with antibiotics that were perceived as less toxic and providing broader antibacterial activity.7 This resulted in aminoglycosides being prescribed for more persistent infections that were resistant to other antibiotics.3 With the amount of antibiotic resistant bacteria increasing, many scientists have begun looking into methods for minimizing aminoglycoside toxicity and maximizing its antibacterial activity.3, 8 These methods include encapsulation and polymer conjugation.9, 10 By encapsulating aminoglycosides in liposomes or other vesicles scientists aim to increase its concentration in infected tissues while decreasing nephro- and ototoxicity.9 With conjugated polymers scientists have created polymer complexes containing aminoglycosides and other compounds such as dopamine.11 The goal of these polymers is to limit toxicity by slowing antibiotic release and increasing efficacy of the antibiotic through targeted delivery and toxicity of other compounds.9, 10, 11 Other than its use in treating infections, aminoglycosides are gaining attention as an excellent vehicle for gene delivery.12 In this application aminoglycosides are used to correct a genetic defect by introducing a normal copy of the gene into affected cells.12,13 Currently scientists are assessing aminoglycosides for gene therapy in the treatment of cancer and various other diseases.12, 14 This review will focus on the diverse customizability of aminoglycosides in treating infections and as vehicles for gene therapy.

ContributorsWampler, Cole (Author) / Rege, Kaushal (Thesis director) / Schoepf, Jared (Committee member) / Barrett, The Honors College (Contributor) / Dean, W.P. Carey School of Business (Contributor) / Chemical Engineering Program (Contributor) / School of Life Sciences (Contributor)
Created2023-05
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Description
Sutures, staples, and tissue glues remain the primary means of tissue approximation and vessel ligation. Laser-activated tissue sealing is an alternative approach that conventionally employs light-absorbing chromophores and nanoparticles for converting near-infrared (NIR) laser to heat. The local increase in temperature engenders interdigitation of sealant and tissue biomolecules, resulting in

Sutures, staples, and tissue glues remain the primary means of tissue approximation and vessel ligation. Laser-activated tissue sealing is an alternative approach that conventionally employs light-absorbing chromophores and nanoparticles for converting near-infrared (NIR) laser to heat. The local increase in temperature engenders interdigitation of sealant and tissue biomolecules, resulting in rapid tissue sealing. Light-activated sealants (LASE) were developed in which indocyanine green (ICG) dye is embedded within a biopolymer matrix (silk or chitosan) for incisional defect repair. Light-activated tissue-integrating sutures (LATIS) that synergize the benefits of conventional suturing and laser sealing were also fabricated and demonstrated higher efficacies for tissue biomechanical recovery and repair in a full-thickness, dorsal surgical incision model in mice compared to commercial sutures and cyanoacrylate skin glue. Localized delivery of modulators of tissue repair, including histamine and copper, from LASE and LATIS further improved healed skin strength. In addition to incisional wounds, histamine co-delivered with silk fibroin LASE films accelerated the closure of full thickness, splinted excisional wounds in immunocompetent BALB/c mice and genetically obese and diabetic db/db mice, resulting in faster closure than Tegaderm wound dressing. Immunohistochemistry analyses showed LASE-histamine treatment enhanced wound repair involving mechanisms of neoangiogenesis, myofibroblast activation, transient epidermal EMT, and also improve healed skin biomechanical strength which are hallmarks of improved healing outcomes. Benefit of temporal delivery was further investigated of a second therapeutic (growth factor nanoparticles) in modulating wound healing outcomes in both acute and diabetic wounds. The hypothesis of temporal delivery of second therapeutic around the ‘transition period’ in wounds further improved wound closure kinetics and biomechanical recovery of skin strength. Laser sealing and approximation, together with delivery of immunomodulatory mediators, can lead to faster healing and tissue repair, thus reducing wound dehiscence, preventing wounds moving towards chronicity and lowering incidence of surgical site infections, all of which can have significant impact in the clinic.
ContributorsGhosh, Deepanjan (Author) / Rege, Kaushal (Thesis advisor) / Acharya, Abhinav (Committee member) / Holloway, Julianne (Committee member) / DiCaudo, David (Committee member) / P. Leung, Kai (Committee member) / Arizona State University (Publisher)
Created2021
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Description

The current clinical gold standards for tissue sealing include sutures, staples, and glues, however several adverse effects limit their use. Sutures and staples inherently cause additional trauma to tissue surrounding the wound, and glues can be lacking in adhesion and are potentially inflammatory. All three also introduce risk of infection.

The current clinical gold standards for tissue sealing include sutures, staples, and glues, however several adverse effects limit their use. Sutures and staples inherently cause additional trauma to tissue surrounding the wound, and glues can be lacking in adhesion and are potentially inflammatory. All three also introduce risk of infection. Light-activated tissue sealing, particularly the use of near-infrared light, is an attractive alternative, as it localizes heat, thereby preventing thermal damage to the surrounding healthy tissue. Previous work identified a glutaraldehyde-crosslinked chitosan film as a lead sealant for gastrointestinal incision sealing, but in vivo testing resulted in tissue degradation in and around the wound. The suggested causes for this degradation were excess acetic acid, endotoxins in the chitosan, and thermal damage. A basic buffer wash protocol was developed to remove excess acid from the films following fabrication. UV-Vis spectroscopy demonstrated that following the wash, films had the same concentration of Indocyanine green as unwashed films, allowing them to absorb light at the same wavelength, therefore showing the wash did not affect the film’s function. However subsequent washes led to degradation of film mass of nearly 20%. Standard chitosan films had significantly greater mass gain (p = 0.028) and significantly less subsequent loss (p= 0.012) than endotoxin free chitosan-films after soaking in phosphate buffered saline for varying durations , while soaking duration had no effect (p = 0.332). Leak pressure testing of films prepared with varying numbers of buffer washes, laser temperature, and lasering time revealed no significant interaction between any of the 3 variables. As such, it was confirmed that proceeding with in vivo testing with the buffer wash, various lasering temperatures, and laser times would not affect the sealing performance of the films. Future investigation will involve characterization of additional materials that may be effective for sealing of internal wounds, as well as drug loading of agents that may hasten the healing process.

ContributorsSira, Antara (Author) / Rege, Kaushal (Thesis director) / Weaver, Jessica (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2022-05
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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
This research reports on the investigation into the synthesis and stabilization of

iron oxide nanoparticles for theranostic applications using amine-epoxide polymers. Although theranostic agents such as magnetic nanoparticles have been designed and developed for a few decades, there is still more work that needs to be done with the type of

This research reports on the investigation into the synthesis and stabilization of

iron oxide nanoparticles for theranostic applications using amine-epoxide polymers. Although theranostic agents such as magnetic nanoparticles have been designed and developed for a few decades, there is still more work that needs to be done with the type of materials that can be used to stabilize or functionalize these particles if they are to be used for applications such as drug delivery, imaging and hyperthermia. For in-vivo applications, it is crucial that organic coatings enclose the nanoparticles in order to prevent aggregation and facilitate efficient removal from the body as well as protect the body from toxic material.

The objective of this thesis is to design polymer coated magnetite nanoparticles with polymers that are biocompatible and can stabilize the iron oxide nanoparticle to help create mono-dispersed particles in solution. It is desirable to also have these nanoparticles possess high magnetic susceptibility in response to an applied magnetic field. The co- precipitation method was selected because it is probably the simplest and most efficient chemical pathway to obtain magnetic nanoparticles.

In literature, cationic polymers such as Polyethylenimine (PEI), which is the industry standard, have been used to stabilize IONPs because they can be used in magnetofections to deliver DNA or RNA. PEI however is known to interact very strongly with proteins and is cytotoxic, so as mentioned previously the Iron Oxide nanoparticles

i

(IONPs) synthesized in this study were stabilized with amine-epoxide polymers because of the limitations of PEI.

Four different amine-epoxide polymers which have good water solubility, biodegradability and less toxic than PEI were synthesized and used in the synthesis and stabilization of the magnetic nanoparticles and compared to PEI templated IONPs. These polymer-templated magnetic nanoparticles were also characterized by size, surface charge, Iron oxide content (ICP analysis) and superconducting quantum interference devices (SQUID) analysis to determine the magnetization values. TEM images were also used to determine the shape and size of the nanoparticles. All this was done in an effort to choose two or three leads that could be used in future work for magnetofections or drug delivery research.
ContributorsTamakloe, Beatrice (Author) / Rege, Kaushal (Thesis advisor) / Kodibagkar, Vikram (Committee member) / Chang, John (Committee member) / Arizona State University (Publisher)
Created2014