Matching Items (7)
Filtering by
- All Subjects: Materials Science
- All Subjects: Bioengineering
- Genre: Academic theses
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 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.
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
Description
Nanoparticles are ubiquitous in various fields due to their unique properties not seen in similar bulk materials. Among them, core-shell composite nanoparticles are an important class of materials which are attractive for their applications in catalysis, sensing, electromagnetic shielding, drug delivery, and environmental remediation. This dissertation focuses on the study of core-shell type of nanoparticles where a polymer serves as the core and inorganic nanoparticles are the shell. This is an interesting class of supramolecular building blocks and can "exhibit unusual, possibly unique, properties which cannot be obtained simply by co-mixing polymer and inorganic particles". The one-step Pickering emulsion polymerization method was successfully developed and applied to synthesize polystyrene-silica core-shell composite particles. Possible mechanisms of the Pickering emulsion polymerization were also explored. The silica nanoparticles were thermodynamically favorable to self-assemble at liquid-liquid interfaces at the initial stage of polymerization and remained at the interface to finally form the shells of the composite particles. More importantly, Pickering emulsion polymerization was employed to synthesize polystyrene/poly(N-isopropylacrylamide) (PNIPAAm)-silica core-shell nanoparticles with N-isopropylacrylamide incorporated into the core as a co-monomer. The composite nanoparticles were temperature sensitive and could be up-taken by human prostate cancer cells and demonstrated effectiveness in drug delivery and cancer therapy. Similarly, by incorporating poly-2-(N,N)-dimethylamino)ethyl methacrylate (PDMA) into the core, pH sensitive core-shell composite nanoparticles were synthesized and applied as effective carriers to release a rheological modifier upon a pH change. Finally, the research focuses on facile approaches to engineer the transition of the temperature-sensitive particles and develop composite core-shell nanoparticles with a metallic shell.
ContributorsSanyal, Sriya (Author) / Dai, Lenore L. (Thesis advisor) / Jiang, Hanqing (Committee member) / Lind, Mary L. (Committee member) / Phelan, Patrick (Committee member) / Rege, Kaushal (Committee member) / Arizona State University (Publisher)
Created2012
Description
Ordered mesoporous materials have tunable pore sizes between 2 and 50 nm and are characterized by ordered pore structures and high surface areas (~1000 m2/g). This makes them particularly favorable for a number of membrane applications such as protein separation, polymer extrusion, nanowire fabrication and membrane reactors. These membranes can be fabricated as top-layers on macroporous supports or as embedded membranes in a dense matrix. The first part of the work deals with the hydrothermal synthesis and water-vapor/oxygen separation properties of supported MCM-48 and a new Al-MCM-48 type membrane for potential use in air conditioning systems. Knudsen-type permeation is observed in these membranes. The combined effect of capillary condensation and the aluminosilicate matrix resulted in the highest separation factor (142) in Al-MCM-48 membranes, with a water vapor permeance of 6×10-8mol/m2Pas. The second part focuses on synthesis of embedded mesoporous silica membranes with helically ordered pores by a novel Counter Diffusion Self-Assembly (CDSA) method. This method is an extension of the interfacial synthesis method for fiber synthesis using tetrabutylorthosilicate (TBOS) and cetyltrimethylammonium bromide (CTAB) as the silica source and surfactant respectively. The initial part of this study determined the effect of TBOS height and humidity on fiber formation. From this study, the range of TBOS heights for best microscopic and macroscopic ordering were established. Next, the CDSA method was used to successfully synthesize membranes, which were characterized to have good support plugging and an ordered pore structure. Factors that influence membrane synthesis and plug microstructure were determined. SEM studies revealed the presence of gaps between the plugs and support pores, which occur due to shrinking of the plug on drying. Development of a novel liquid deposition method to seal these defects constituted the last part of this work. Post sealing, excess silica was removed by etching with hydrofluoric acid. Membrane quality was evaluated at each step using SEM and gas permeation measurements. After surfactant removal by liquid extraction, the membranes exhibited an O2 permeance of 1.65x10-6mol/m2.Pa.s and He/O2 selectivity of 3.30. The successful synthesis of this membrane is an exciting new development in the area of ordered mesoporous membrane technology.
ContributorsSeshadri, Shriya (Author) / Lin, Jerry Y. S. (Thesis advisor) / Dai, Lenore (Committee member) / Rege, Kaushal (Committee member) / Smith, David J. (Committee member) / Vogt, Bryan (Committee member) / Arizona State University (Publisher)
Created2011
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 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
Description
The use of mRNA for therapeutic purposes has gained significant attention due to its potential to treat a wide range of diseases, including cancer, infectious diseases, and genetic disorders. However, the efficient delivery of mRNA to target cells remains a major challenge, and delivery of mRNA faces major issues such as rapid degradation and poor cellular uptake. Aminoglycoside-derived lipopolymer nanoparticles (LPNs) have been shown as a promising platform for plasmid DNA (pDNA) delivery due to their stability, biocompatibility, and ability to encapsulate mRNA. The current study aims to develop and optimize LPNs formulation for the delivery of mRNA in aggressive cancer cells, using a combination of chemical synthesis, physicochemical characterization, and in vitro biological assays. From a small library of aminoglycoside-derived lipopolymers, the lead lipopolymers were screened for the efficient delivery of mRNA. The complexes were synthesized with different ratios of lipopolymers to mRNA. The appropriate binding ratios of lipopolymers and mRNA were determined by gel electrophoresis. The complexes were characterized using dynamic light scattering (DLS) and zeta potential. The transgene expression efficacy of polymers was evaluated using in vitro bioluminescence assay. The toxicity of LPNs and LPNs-mRNA complexes was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The current study comprehensively investigates the optimization of the LPNs-mRNA formulation for enhanced efficacy in transgene expression in human advanced-stage melanoma cell lines.
ContributorsWubhayavedantapuram, Revanth (Author) / Rege, Kaushal (Thesis advisor) / Acharya, Abhinav (Committee member) / Yaron, Jordan (Committee member) / Arizona State University (Publisher)
Created2023
Description
Combining 3D bio-printing and drug delivery are promising techniques tofabricate scaffolds with well controlled and patient-specific structures for tissue
engineering. In this study, silk derivatives of bioink were developed consisting of
silk fibroin and gelatin then 3D printed into scaffolds. The scaffolds would be
evaluated for small molecule release, cell growth, degradation, and morphology.
Preparations and design of the scaffolds are major parts of engineering and tissue
engineering. Scaffolds are designed to mimic extracellular matrix by providing
structural support as well as promoting cell attachment and proliferation with
minimum inflammation while degrading at a controlled rate. Scaffolds offers new
potentials in medicine by aiding in the preparation of personalized and controlled
release therapeutic systems.
ContributorsNg, Johnny (Author) / Rege, Kaushal (Thesis advisor) / Holloway, Julianne (Committee member) / Jin, Kailong (Committee member) / Arizona State University (Publisher)
Created2022
Description
Drug delivery has made a significant contribution to cancer immunotherapy and can have a tremendous impact on modulating immunometabolism, thereby affecting cancer outcomes. Notably, the science of delivery of cancer vaccines and immunotherapeutics, modulating immune cell functions has inspired development of several successful companies and clinical products. For example, cancer vaccines require activation of dendritic cells (DCs) and tumour associated Mɸs (TAMs) through modulation of their energy metabolism (e.g., glycolysis, glutaminolysis, Krebs cycle). Similar to activated immune cells, cancer cells also upregulate glucose and glutamine transporters for proliferation and survival. Cancer cells having accelerated energy metabolism, which has been exploited as a target for various therapeutic studies. In the first strategy, an immunometabolism strategy based on sustained release of succinate from biomaterials, which incorporate succinate in the backbone of the polymer was developed. This study demonstrates that succinate-based polymeric microparticles act as alarmins by modulating the immunometabolism of DCs and Mɸs to generate robust pro-inflammatory responses for melanoma treatment in immunocompetent young as well as aging mice. In the second strategy, a biomaterial-based strategy was developed to deliver metabolites one-step downstream of the node where the glycolytic pathway is inhibited, to specifically rescue DCs from glycolysis inhibition. The study successfully demonstrated for the first time that the glycolysis of DCs can be rescued both in vitro and in vivo using a biomaterial strategy of delivering metabolites downstream of the inhibitory node. Overall, it is believed that advanced drug delivery strategies will play an important role in marrying the fields of immunometabolism and immunotherapy to generate translatable anti-cancer treatments.
ContributorsInamdar, Sahil (Author) / Acharya, Abhinav P (Thesis advisor) / Rege, Kaushal (Committee member) / Green, Matthew (Committee member) / Curtis, Marion (Committee member) / Seetharam, Mahesh (Committee member) / Arizona State University (Publisher)
Created2022