A. James Clark School of Engineering
Permanent URI for this communityhttp://hdl.handle.net/1903/1654
The collections in this community comprise faculty research works, as well as graduate theses and dissertations.
Browse
13 results
Search Results
Item ENGINEERING TARGETED LIGHT ACTIVATABLE NANOPLATFORMS TO MANAGE RECURRENT CANCERS(2024) Pang, Sumiao; Huang, Huang Chiao HH; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Cancer recurrence poses a significant challenge in various malignancies that adverselyaffect long-term survival and quality of life. Glioblastoma (GBM) and ovarian cancer exhibit particularly high recurrence rates. For GBM, tumor recurrence is nearly universal (90%) within 10 months post initial treatment due to its invasive characteristics, limited delivery of therapeutic agents, and persistent drug resistance, resulting in a 5-year survival rate of <10%. While standard chemotherapy and surgery can temporarily alleviate symptoms for both diseases, there has been no significant improvement in long-term disease management or survival extension over several decades. Therefore, it is critical to develop targeted therapies that integrates well with current standards of care strategies. Photomedicine is a promising treatment modality, and the two main phototherapies are photodynamic therapy (PDT) which involves photosensitizer administration followed by light activation resulting in non-thermal chemical damage and photothermal therapy (PTT) which involves exogenous or endogenous sensitizing agents followed by light activation resulting in thermal damage. Clinical applications of both modalities have shown its feasibility and safety; however, they face challenges due to (i) limited cancer selectivity, (ii) heterogenous treatment response, and (iii) low monotherapy treatment efficacy. Leveraging strategic therapeutic targets to advance the current sensitizing agents for targeted delivery is a potential solution to overcome these limitations. The overall objective of this dissertation is to advance and evaluate targeted light-activatable nanoplatforms for phototherapy delivery with considerations for the current clinical workflow of GBM and advanced ovarian cancer. This is achieved through the following goals, (1) engineering a novel Fn14 receptor-directed gold nanorods (DART-GNRs) to assess selectivity and PTT efficacy for GBM, and (2) evaluate safety and long-term efficacy of targeted light-activatable multi-agent nanoplatform (tLAMP) to deliver targeted PDT for peritoneal carcinomatosis. First, this work establishes a reproducible synthesis protocol for DART-GNRs, characterizes its photothermal properties, and demonstrate high selectivity towards the Fn14 receptor of cancer cells. Second half of this dissertation established and investigated a two-fiber tissue optical property (TOP) monitoring method for liquid phantoms and for peritoneal carcinomatosis mouse model to enable safer light dosimetry during PDT, established an irinotecan active loading method to reproducibly synthesize tLAMP, and determined tLAMP tumor nodule penetration depth for enhanced targeted PDT combination therapy with adjuvant chemotherapy to enhance long-term survival for ovarian cancer.Item DEVELOPMENT OF GLYCOSAMINOGLYCAN MIMICKING NANOGEL TECHNOLOGIES FOR CONTROLLED RELEASE OF THERAPEUTICS TO TREAT RETINAL DISEASES IN DIFFERENT AGE GROUPS(2024) Kim, Sangyoon; Lowe, Tao L.; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Retinal diseases, such as diabetic retinopathy, glaucoma, macular degeneration, and retinoblastoma, affect around 13 million people worldwide, with projections indicating a rise to 20 million by 2030. These conditions lead to irreversible vision loss and significant impairment in both adults and children, with an annual economic burden of $139 billion in the United States alone. Aging significantly increases the risk of certain retinal conditions, and with improvements in healthcare leading to increased life expectancy, these conditions are becoming more prevalent due to the natural aging process and associated physiological changes in the eye. Current treatments are either destructive or have low efficacy and are not optimized for the younger population. While therapeutics including small molecular drugs, proteins and antibodies show promise in treating these diseases by reducing inflammation and neuronal apoptosis, their effectiveness is hindered by short half-lives and inability to cross the blood-retinal barrier (BRB). Nanoparticles offer a potential solution by improving drug delivery across biological barriers, yet no nanoparticles have been developed to effectively transport intact proteins or small molecules across the BRB to the retina without toxicity, slow clearance and stability. Therefore, there is an unmet need to evaluate the physical and physiological property changes of the eye along development and develop nanoparticle systems that can control and sustain the release of therapeutics across the blood retinal barrier (BRB) to treat the retinal diseases. In this project, the thickness, rheological property, permeability and morphological property changes of ocular barriers including sclera, cornea and vitreous humor in the developing eye from preterm to adult were evaluated using porcine ex vivo model. Two glycosaminoglycan mimicking nanogel systems, poly(NIPAAm-co-DEXcaprolactoneHEMA) nanogels with and without positive or negative charges and β-cyclodextrin based poly(β-amino ester) (CD-p-AE) nanogels were developed for sustained release of intact proteins including insulin and anti-TNFα, and small hydrophobic drugs, respectively across the ex vivo porcine sclera and in vitro BRB models: human fetal retinal pigment epithelial (hfRPE), adult retinal pigment epithelial (ARPE-19) and human cerebral microvascular endothelial (hCMEC/D3) cell monolayers. Completion of this project will have a significant impact on developing novel personalized nanotherapeutics to treat retinal diseases in different age groups.Item Recent Advancements in Mitochondria-Targeted Nanoparticle Drug Delivery for Cancer Therapy(MDPI, 2022-02-23) Xu, Jiangsheng; Shamul, James G.; Kwizera, Elyahb Allie; He, XiaomingMitochondria are critical subcellular organelles that produce most of the adenosine triphosphate (ATP) as the energy source for most eukaryotic cells. Moreover, recent findings show that mitochondria are not only the “powerhouse” inside cells, but also excellent targets for inducing cell death via apoptosis that is mitochondria-centered. For several decades, cancer nanotherapeutics have been designed to specifically target mitochondria with several targeting moieties, and cause mitochondrial dysfunction via photodynamic, photothermal, or/and chemo therapies. These strategies have been shown to augment the killing of cancer cells in a tumor while reducing damage to its surrounding healthy tissues. Furthermore, mitochondria-targeting nanotechnologies have been demonstrated to be highly efficacious compared to non-mitochondria-targeting platforms both in vitro and in vivo for cancer therapies. Moreover, mitochondria-targeting nanotechnologies have been intelligently designed and tailored to the hypoxic and slightly acidic tumor microenvironment for improved cancer therapies. Collectively, mitochondria-targeting may be a promising strategy for the engineering of nanoparticles for drug delivery to combat cancer.Item Functionally Coated Faceted Aluminum Nanocrystals: Aerosol Synthesis and Reactivity(2013) Kaplowitz, Daniel Alan; Zachariah, Michael R; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The demand for large scale manufacture of nanoaluminum for use in propellant applications has motivated research into development of an aerosol production scheme. In addition, the reactive nature of aluminum in the presence of oxygen has inspired investigation into functionally coating bare nanoaluminum prior to exposure to the atmosphere. Faceted aluminum crystals are fabricated in the aerosol phase via thermal pyrolysis of triisobutylaluminum, a low temperature gas-phase synthesis route, and combustion tests of oxygen passivated product in thermite combination show an increase in energy release compared to commercial nanoaluminum. Three different coatings on this bare nanoaluminum are developed: a decoration of Ni/Ni2O3 particles by thermal decomposition of Ni(CO)4, a homogeneous layer of Fe3O4 by thermal decomposition of Fe(CO)5, and a monolayer of perfluoropentanoic acid via bridge bonding between aluminum and carboxylate groups. X-ray photoelectron spectroscopy analysis indicates that the metal oxide coatings have facilitated formation of an expanded aluminum oxide layer during an air bleed, but perfluoropentanoic acid has successfully passivated aluminum. The protection from significant oxide formation for the perfluoropentanoic acid coating is evident in a 16% increase in active fuel content by thermogravimetric analysis compared to the untreated case. Subsequent temperature jump fine wire combustion tests show decreased ignition temperatures for all three coatings. Combustion chamber tests in thermite combinations display poor pressure output for the Ni/Ni2O3 coated case, but reasonable response for the Fe3O4 product. Flame ignition of perfluoropentanoic acid coated product is shown to produce AlF3 by chemical analysis of char, indicating the passivation coating also functions in direct oxidizer delivery.Item Magnetic Drug Targeting: Developing the Basics(2013) Nacev, Aleksandar Nelson; Shapiro, Benjamin; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Focusing medicine to disease locations is a needed ability to treat a variety of pathologies. During chemotherapy, for example, typically less than 0.1% of the drugs are taken up by tumor cells, with the remaining 99.9% going into healthy tissue. Physicians often select the dosage by how much a patient can physically withstand rather than by how much is needed to kill all the tumor cells. The ability to actively position medicine, to physically direct and focus it to specific locations in the body, would allow better treatment of not only cancer but many other diseases. Magnetic drug targeting (MDT) harnesses therapeutics attached to magnetizable particles, directing them to disease locations using magnetic fields. Particles injected into the vasculature will circulate throughout the body as the applied magnetic field is used to attempt confinement at target locations. The goal is to use the reservoir of particles in the general circulation and target a specific location by pulling the nanoparticles using magnetic forces. This dissertation adds three main advancements to development of magnetic drug targeting. Chapter 2 develops a comprehensive ferrofluid transport model within any blood vessel and surrounding tissue under an applied magnetic field. Chapter 3 creates a ferrofluid mobility model to predict ferrofluid and drug concentrations within physiologically relevant tissue architectures established from human autopsy samples. Chapter 4 optimizes the applied magnetic fields within the particle mobility models to predict the best treatment scenarios for two classes of chemotherapies for treating future patients with hepatic metastatic breast cancer microtumors.Item COPPER OXIDE NANOARCHITECTURES FOR PHOTOELECTROCHEMICAL HYDROGEN GENERATION(2012) Chiang, Chia-Ying; Ehrman, Sheryl H; Chemical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Hydrogen is a high-quality energy carrier, similar to electricity, which can be used with high efficiency and near-zero emissions at the point of use. The most promising means of producing hydrogen using a renewable energy source and potentially reducing the generation of greenhouse gases production is through solar-hydrogen photoelectrochemical (PEC) water decomposition. In order to utilize the solar irradiation, small band gap material is essential. In this dissertation, I focus on the earth abundant, non-toxic and direct transit copper oxide (CuO) with band gap around 1.3-1.8 eV. In a PEC cell, the photo-excited charge carriers need to be separated as soon as they form in order to have a high photocurrent density. Thus, four approaches are studied: (1) decrease particle size to decrease the electron-hole recombination in the particles, (2) increase surface area to increase the active sites and decrease the distance for electrons travel to the surface to react with water (3) increase conductivity to decrease the resistance of the electrode, and (4) shorten charge carrier transport distance to decrease the chance of recombination of charge carriers. In the first part of this study, I describe the aerosol route, flame spray pyrolysis, for making CuO nanoparticles. By controlling the precursor concentration and flame conditions, the particle size can be tuned. Also, the simulation results of particle growth, based on collision/sintering theory with sintering by solid state diffusion, are in good agreement with the experimental results. Furthermore, the flame spray pyrolysis made CuO nanoparticles were spin coated on conducting ITO glass substrates for the PEC study. Here, the relatively uniform CuO nanoparticles showed much better photocurrent density compared to the commercial CuO nanoparticles with a broad size distribution. This demonstrates the importance of the size of material for PEC application. The second approach I introduced is to increase surface area to increase the active sites. Instead of changing the CuO suspension concentration to make films with different porosity, I present a new route for forming porous structures by spin coating the powder including CuO and its intermediate product, Cu2(NO3)(OH)3. During the post annealing process, the intermediate product transforms into CuO and leaves voids in the film, thus producing a porous film and increasing the active surface area for the water splitting reaction. In the third approach, lithium was incorporated as a dopant to increase conductivity and decrease the resistance of the electrode. With the lithium added, the conductivity increased by two orders of magnitude and thus highly decreased the film resistance and increased the photocurrent density. The final part of this dissertation focuses on three dimensional current collectors, used to decrease the charge carrier transport distance and thus decrease the chance of recombination. Here, the genetically modified tobacco mosaic virus (TMV1cys) served as a template for the three dimensional structure, made by sputter deposition of CuO. By varying the virus concentration, the distance between the current collectors can be tuned to optimize the charge carrier transport distance, light reflection as well as the CuO thickness for efficient absorption of solar energy.Item Lipid-Hydrogel Nanoparticles: Synthesis Methods and Characterization(2009) Hong, Jennifer S.; Raghavan, Srinivasa R; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)This dissertation focuses on the directed self-assembly of nanoscale soft matter particles using methods based on liposome-templating. Nanoscale liposomes, nano-sized hydrogel particles ("nanogels"), and hybrids of the two have enormous potential as carriers in drug delivery and nanotoxicity studies, and as nanovials for enzyme encapsulation and single molecule studies. Our goal is to develop assembly methods that produce stable nanogels or hybrid lipid-polymer nanoparticles, using liposomes as size and shape templates. First we describe a bulk method that employs liposomes to template relatively monodisperse nanogels composed of the biopolymer, alginate, which is a favorable material for nanogel formation because it uses a gentle ionic crosslinking mechanism that is suitable for the encapsulation of cells and biomolecules. Liposomes encapsulating sodium alginate are suspended in aqueous buffer containing calcium chloride, and thermal permeabilization of the lipid membrane facilitates transmembrane diffusion of Ca2+ ions from the surrounding buffer into the intraliposomal space, ionically crosslinking the liposome core. Subsequent lipid removal results in bare calcium alginate nanogels with a size distribution consistent with that of their liposome template. The second part of our study investigates the potential for microfluidic-directed formation of lipid-alginate hybrid nanoparticles by adapting the above bulk self-assembly procedure within a microfluidic device. Specifically we investigated the size control of alginate nanogel self-assembly under different flow conditions and concentrations. Finally, we investigate the microfluidic directed self-assembly of lipid-polymer hybrid nanoparticles, using phospholipids and an N-isopropylacrylamide monomer as the liposome and hydrogel precursors, respectively. Microfluidic hydrodynamic focusing is used to control the convective-diffusive mixing of the two miscible nanoparticle precursor solutions to form nanoscale vesicles with encapsulated hydrogel precursor. The encapsulated hydrogel precursor is polymerized off-chip and the resultant hybrid nanoparticle size distributions are highly monodisperse and precisely controlled across a broad range relevant to the targeted delivery and controlled release of encapsulated therapeutic agents. Given the ability to modify liposome size and surface properties by altering the lipid components and the many polymers of current interest for nanoparticle synthesis, this approach could be adapted for a variety of hybrid nanoparticle systems.Item GAS PHASE SYNTHESIS OF ALUMINUM AND CORE-SHELL NICKEL-IRON OXIDE NANOPARTICLES(2009) Pines, Daniel; Zachariah, Michael; Material Science and Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)In this master's thesis I will address the design of two aluminum and one nickel-iron oxide core-shell nanoparticle reactors, as well as the selection of the chemical precursors' triethylaluminum (TEA), aluminum trichloride, nickel carbonyl, and iron pentacarbonyl. This research provides evidence for the generation of aluminum oxide passivated aluminum nanoparticles from TEA, the failure to completely dissociate aluminum trichloride, and the successful growth of iron oxide (shell) onto nickel (core) nanoparticles. Reactions and synthesis are carried out in gas phase allowing the use of specialized aerosol sampling and characterization techniques. In addition to studying the particle in situ, TEM and EDS measurements are preformed post collection. Motivation for this work is driven by the nanoparticle's enhanced performance when used in explosive and propellants.Item Controlled liposome formation and solute encapsulation with continuous-flow microfluidic hydrodynamic focusing(2008-12-11) Jahn, Andreas; DeVoe, Don L; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Liposomes enable the compartmentalization of compounds making them interesting as drug delivery systems. A drug delivery system (DDS) is a transport vehicle for a drug for in vivo drug administration. Drugs can be encapsulated, bound, or otherwise tethered to the carrier which can vary in size from tens of nanometers to a few micrometers. Liposomal DDSs have shown their capability to deliver drugs in a new fashion, allowing exclusive sales of encapsulated drugs to be extended beyond the initial compound's patent expiration date. However, existing methods to form liposomes and encapsulate drugs are based on bulk mixing techniques with limited process control and the produced liposomes frequently require post-processing steps. In this dissertation, a new method is demonstrated to control liposome formation and compound encapsulation that pushes beyond existing benchmarks in liposome size homogeneity and adjustable encapsulation. The technology utilizes microfluidics for future pharmacy-on-a-chip applications. The microfluidic system allows for precise control of mixing via molecular diffusion with reproducible and controlled physicochemical conditions compared to traditional bulk-phase preparation techniques (i.e. test tubes and beakers). The laminar flow and facile fluidic control in microchannels enables reproducible self-assembly of lipids into liposomes in a sheathed flow-field. Confining a water-soluble compound to be encapsulated to the immediate vicinity where liposome formation is expected to occur reduces sample consumption without affecting liposome loading. The ability to alter the concentration and control the amount of encapsulated compounds within liposomes in a continuous-flow mode is another interesting feature towards tailored liposomal drug delivery. The liposome formation strategy demonstrated in this dissertation offers potential for point-of-care drug encapsulation, eliminating shelf-life limitations inherent to current liposome preparation techniques.Item Numerical Study of Plasmon Resonances in Nanoparticles(2007-11-28) Zhang, Zhenyu; MAYERGOYZ, ISAAK D; Electrical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Surface plasmon resonances in nanoparticles have numerous promising scientific and technological applications in such areas as nanophotonics, near-field microscopy, nano-lithography, biosensor, metamaterial and optical data storage. Consequently, the understanding of plasmon resonances in nanoparticles has both fundamental and practical significance. In this dissertation, a new numerical technique to fully characterize the plasmon resonances in three-dimensional nanoparticles is presented. In this technique, the problem of determining the plasmon resonant frequencies is framed as an integral equation based eigenvalue problem, and the plasmon resonant frequencies can be directly found through the solution of this eigenvalue problem. For this reason, it is computationally more efficient than other "trial-and-error" numerical techniques such as the finite-difference time-domain (FDTD) method. This boundary integral equation method leads to fully populated discretized matrix equations that are computationally expensive to solve, especially when a large number of particles are involved in the nanostructures. Since the fully populated matrices are generated by integrals with 1/r-type kernel, this computational problem is appreciably alleviated by using the fast multipole method (FMM). The boundary integral approach is also extended to the calculation of the extinction cross sections of nanoparticles, which reveal important information such as the strength and the full width at half maximum (FWHM) of these resonances. The numerical implementation of this technique is discussed in detail and numerous computational results are presented and compared with available theoretical and experimental data. Furthermore, metallic nanoshells for biosensing applications as well as nanoparticle-structured plasmonic waveguides of light are numerically investigated. The integral equation based numerical technique presented throughout this dissertation can be instrumental for the design of plasmon resonant nanoparticles and to tailor their optical properties for various applications.