Matching Items (5)
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- All Subjects: Nanoparticles
- Creators: Vernon, Brent
- Creators: Acharya, Abhinav
- Status: Published
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
Achieving effective drug concentrations within the central nervous system (CNS) remains one of the greatest challenges for the treatment of brain tumors. The presence of the blood-brain barrier and blood-spinal cord barrier severely restricts the blood-to-CNS entry of nearly all systemically administered therapeutics, often leading to the development of peripheral toxicities before a treatment benefit is observed. To circumvent systemic barriers, intrathecal (IT) injection of therapeutics directly into the cerebrospinal fluid (CSF) surrounding the brain and spinal cord has been used as an alternative administration route; however, its widespread translation to the clinic has been hindered by poor drug pharmacokinetics (PK), including rapid clearance, inadequate distribution, as well as toxicity. One strategy to overcome the limitations of free drug PK and improve drug efficacy is to encapsulate drug within nanoparticles (NP), which solubilize hydrophobic molecules for sustained release in physiological environments. In this thesis, we will develop NP delivery strategies for brain tumor therapy in two model systems: glioblastoma (GBM), the most common and deadly malignant primary brain tumor, and medulloblastoma, the most common pediatric brain tumor. In the first research chapter, we developed 120 nm poly(lactic acid-co-glycolic acid) NPs encapsulating the chemotherapy, camptothecin, for intravenous delivery to GBM. NP encapsulation of camptothecin was shown to reduce the drug’s toxicity and enable effective delivery to orthotopic GBM. To build off the success of intravenous NP, the second research chapter explored the utility of 100 nm PEGylated NPs for use with IT administration. Using in vivo imaging and ex vivo tissue slices, we found the NPs were rapidly transported by the convective forces of the CSF along the entire neuraxis and were retained for over 3 weeks. Based on their wide spread delivery and prolonged circulation, we examine the ability of the NPs to localize with tumor lesions in a leptomeningeal metastasis (LM) model of medulloblastoma. NPs administered to LM bearing mice were shown to penetrate into LM mets seeded within the meninges around the brain. These data show the potential to translate our success with intravenous NPs for GBM to improve IT chemotherapy delivery to LM.
ContributorsHouseholder, Kyle Thomas (Author) / Sirianni, Rachael W. (Thesis advisor) / Stabenfeldt, Sarah (Committee member) / Vernon, Brent (Committee member) / Caplan, Michael (Committee member) / Wechsler-Reya, Robert (Committee member) / Arizona State University (Publisher)
Created2018
Description
This report provides information concerning qualities of methylcellulose and how those properties affect further experimentation within the biomedical world. Utilizing the compound’s biocompatibility many issues, ranging from surgical to cosmetic, can be solved. As of recent, studies indicate, methylcellulose has been used as a physically cross-linked gel, which cannot sustain a solid form within the body. Therefore, this report will ultimately explore the means of creating a non-degradable, injectable, chemically cross-linking methylcellulose- based hydrogel. Methylcellulose will be evaluated and altered in experiments conducted within this report and a chemical cross-linker, developed from Jeffamine ED 2003 (O,O′-Bis(2-aminopropyl) polypropylene glycol-block-polyethylene glycol-block-polypropylene glycol), will be created. Experimentation with these elements is outlined here, and will ultimately prompt future revisions and analysis.
ContributorsBundalo, Zoran Luka (Author) / Vernon, Brent (Thesis director) / LaBelle, Jeffrey (Committee member) / Overstreet, Derek (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2013-05
Scaled Formulations of Succinate based Polymeric particles for Eventual Testing in Clinical Settings
Description
With an estimated 19.3 million cases and nearly 10 million deaths from cancer in a year worldwide, immunotherapies, which stimulate the immune system so that it can attack and kill cancer cells, are of interest. Tumors are produced from the uncontrolled and rapid proliferation of cells in the body. Cancer cells rely heavily on glutamine for proliferation due to its contribution of nitrogen for nucleotides and amino acids. Glutamine enters the tricarboxylic acid (TCA) cycle as α-ketoglutarate via glutaminolysis, in which glutamine is converted into glutamate by the enzyme glutaminase (GLS). Cancer cell proliferation may be limited by using glutaminase inhibitor CB-839. However, immune cells also rely on these metabolic pathways. Thus, a method for restarting the metabolic pathways in the presence of inhibitors is attractive. Succinate, a key metabolite in the TCA cycle, has been shown to stimulate the immune system despite the presence of metabolic inhibitors, such as CB-839. A delivery method of succinate is through microparticles (MPs) or nanoparticles (NPs) which may be coated in polyethylene glycol (PEG) for improved hydrophilicity. Polyethylene glycol succinate (PEGS) MPs were generated and tested in vivo and were shown to reduce tumor growth and prolong mouse survival. With the success in stimulating the immune system with MPs, NPs were investigated for an improved immune response due to their smaller size. These PES NPs were generated in this study. For clinical settings, it is necessary to scale-up the production of particles. Two methods of scale-up were proposed: (1) a combination of multiple small batches into a mixed batch, and (2) a singular, big batch. Size and release properties were compared to a small batch of PES NPs, and it was concluded that the big batch more closely resembled the small batch compared to the mixed batch. Thus, it was concluded that batch-to-batch variability plays a larger role than volume changes when scaling-up. In clinical settings, it is recommended to produce the particles in a big batch rather than a mixed batch.
ContributorsSundem, Alison (Author) / Acharya, Abhinav (Thesis director) / Inamdar, Sahil (Committee member) / Barrett, The Honors College (Contributor) / School of Molecular Sciences (Contributor) / Chemical Engineering Program (Contributor)
Created2023-05
Description
Tissue approximation and repair have been performed with sutures and staples for centuries, but these means are inherently traumatic. Tissue repair using laser-responsive nanomaterials can lead to rapid tissue sealing and repair and is an attractive alternative to existing clinical methods. Laser tissue welding is a sutureless technique for sealing incised or wounded tissue, where chromophores convert laser light to heat to induce in tissue sealing. Introducing chromophores that absorb near-infrared light creates differential laser absorption and allows for laser wavelengths that minimizes tissue damage.
In this work, plasmonic nanocomposites have been synthesized and used in laser tissue welding for ruptured porcine intestine ex vivo and incised murine skin in vivo. These laser-responsive nanocomposites improved tissue strength and healing, respectively. Additionally, a spatiotemporal model has been developed for laser tissue welding of porcine and mouse cadaver intestine sections using near-infrared laser irradiation. This mathematical model can be employed to identify optimal conditions for minimizing healthy cell death while still achieving a strong seal of the ruptured tissue using laser welding. Finally, in a model of surgical site infection, laser-responsive nanomaterials were shown to be efficacious in inhibiting bacterial growth. By incorporating an anti-microbial functionality to laser-responsive nanocomposites, these materials will serve as a treatment modality in sealing tissue, healing tissue, and protecting tissue in surgery.
In this work, plasmonic nanocomposites have been synthesized and used in laser tissue welding for ruptured porcine intestine ex vivo and incised murine skin in vivo. These laser-responsive nanocomposites improved tissue strength and healing, respectively. Additionally, a spatiotemporal model has been developed for laser tissue welding of porcine and mouse cadaver intestine sections using near-infrared laser irradiation. This mathematical model can be employed to identify optimal conditions for minimizing healthy cell death while still achieving a strong seal of the ruptured tissue using laser welding. Finally, in a model of surgical site infection, laser-responsive nanomaterials were shown to be efficacious in inhibiting bacterial growth. By incorporating an anti-microbial functionality to laser-responsive nanocomposites, these materials will serve as a treatment modality in sealing tissue, healing tissue, and protecting tissue in surgery.
ContributorsUrie, Russell Ricks (Author) / Rege, Kaushal (Thesis advisor) / Acharya, Abhinav (Committee member) / DeNardo, Dale (Committee member) / Holloway, Julianne (Committee member) / Thomas, Marylaura (Committee member) / Arizona State University (Publisher)
Created2019