Master of Science (MS), Wright State University, 2019, Chemistry

The number of consumer products containing nanomaterials over the last eight years has increased over two-fold. Silver is one of the most commonly used materials in consumer goods nanoparticle fabrication.1 Thus, the uptake and biodistribution of silver nanoparticles (AgNPs) within mammalian cells can provide insight into their possible toxicological effects. In this study, starch-capped AgNPs of an average diameter of 9 ± 5 nm were synthesized via a bottom-up method, and characterized by Raman spectroscopy, transmission electron microscopy (TEM), inductively couple plasma optical emission spectroscopy (ICP-OES), and absorption spectroscopy. Vero 76 cells were incubated with 0.0, 0.1, 1.0, and 3.0 mg/L starch-capped AgNPs for 2, 4, 12, and 24 hr in a water vehicle control for imaging with CytoViva darkfield microscopy and hyperspectral analysis. It was observed that the morphology of the cells was negatively impacted at all exposure concentrations in a dose-dependent manner. The cells appear clustered, had fewer dendrites forming, and cell debris is visible on the microscope slide. Vero 76 cells were exposed to all concentrations of AgNPs for 4 hr at 0.0, 0.1, 1.0, and 1.5 mg/L for mitochondrial isolation and total Ag uptake was estimated by ICP-OES. It was determined that at exposure concentrations of 1.0 and 1.5 mg/L, AgNPs remained in the incubated Dulbecco's Modified Eagle Medium (DMEM), 86% and 77%, respectively. A bicinchoninic acid (BCA) protein assay was also performed under similar conditions in order to examine cell viability. Cellular toxicity was found to be concentration dependent; the smallest cell viability value (7%) was observed at the highest concentration of AgNPs (3 mg/L).

Committee: Ioana E. Pavel Ph.D. (Advisor); David A. Dolson Ph.D. (Committee Member); Steven R. Higgins Ph.D. (Committee Member); Marjorie M. Markopoulos Ph.D. (Committee Member) Subjects: Chemistry; Nanotechnology

Doctor of Philosophy (PhD), Wright State University, 2017, Biomedical Sciences PhD

Silver nanoparticles (AgNPs) and ionic silver (Ag+) are known to be broad-spectrum antimicrobial agents. Recent studies show these agents may be an alternative to the most widely used drinking water disinfectant, chlorine. Chlorine is a toxic industrial chemical with a lethal concentration of 430 ppm after 30 minutes. Additionally, chlorine can react with naturally occurring materials to produce a number of disinfection byproducts such as chloroform and trihalomethanes. Some of these byproducts pose cancer risks in addition to other negative impacts to human health. These would be eliminated with the use of Ag+ or AgNPs. The main goal of this study was to show the less-explored electrochemically-synthesized silver colloid (eAg) is more effective than widely-used borohydride-capped silver nanoparticles (bAg) against the Gram-negative and water quality organisms (Escherichia coli, Klebsiella variicola, and Pseudomonas aeruginosa) at similar bacterial concentrations (e.g., 5x105 CFU mL-1) and at 0.1 mg L-1 silver, the secondary contaminant limit for drinking water. Silver colloids (eAg and bAg) were synthesized, concentrated, fractionated (5-17 nm), and their corresponding physico-chemical properties were determined and compared (e.g., size distribution, shape, surface chemistry and area). The minimum inhibitory concentration (MIC) and minimum bactericidal concentrations (MBC) for bacterial concentrations (5x105 CFU mL-1) were approximately 10 times lower for the eAg (approximately 3 mg L-1, 4 mg L-1) than bAg (approximately 35 mg L-1). These results were compared to the dose-dependent effect on bacterial concentration for the AgNPs at a steady concentration of 0.1 mg L-1, the health advisory level where no risk to health would be observed. The three types of bacteria exhibited a similar response to the three test agents, i.e., Ag+ was most effective, followed by eAg, and lastly bAg. These studies show that eAg is more effective than bAg and the antibacterial effective (open full item for complete abstract)

Committee: Ioana Sizemore Ph.D. (Committee Chair); Nicholas Reo Ph.D (Committee Member); Michael Raymer Ph.D. (Committee Member); David Dolson Ph.D. (Committee Member); Jason Deibel Ph.D. (Committee Member) Subjects: Biomedical Research; Chemistry; Microbiology; Nanoscience; Nanotechnology

PhD, University of Cincinnati, 2016, Engineering and Applied Science: Chemical Engineering

Nanotechnology has undergone a dramatic increase in popularity in the last decade due to the unique physicochemical characteristics of engineered nanomaterials (ENMs). Currently, approximately a quarter of all nano-enabled consumer products contain silver nanoparticles (AgNPs). AgNPs are incorporated into a wide range of consumer products (e. g., textiles, filters, disinfectants, and washing machines) and have a wide range of medical, industrial and scientific applications. The increased application of AgNPs will inevitably lead to their release into environmental systems. Since the presumed mechanisms governing the fate, transport and toxicity of matter at the bulk scale may not directly apply to nanomaterials, the potential environmental impacts associated with the release of AgNPs must be evaluated. Furthermore, AgNPs are manufactured with a wide range of physicochemical properties that impact their fate, transport and toxicity in the environment. To this end, the impact of silver nanoparticles on the composting of municipal solid waste was evaluated. Neither the presence of AgNPs nor the presence of Ag+ had a statistically significant influence on leachate, gas and solid quality parameters, and therefore, on overall composting performance. However, AgNPs and Ag+ both changed the overall structure of the bacterial communities within the compost. Nevertheless, the functional performance of the composting process was not significantly affected due to the abundance and functional redundancy of the bacterial communities within the compost samples. While surface transformations of AgNPs to AgCl and Ag2S reduce toxicity, complexation with organic matter may also play a role. The results of this study further suggest that at relatively low concentrations of AgNPs, these organically rich waste management systems can withstand the presence of AgNPs. The microbial toxicity of silver nanoparticles stabilized with different capping agents were evaluated under anaer (open full item for complete abstract)

Committee: Stephen Thiel Ph.D. (Committee Chair); Thabet Tolaymat Ph.D. (Committee Member); Vadim Guliants Ph.D. (Committee Member); Vesselin Shanov Ph.D. (Committee Member); George Sorial Ph.D. (Committee Member) Subjects: Chemical Engineering

Doctor of Philosophy (Ph.D.), University of Dayton, 2011, Biology

1: Silver nanoparticles (Ag Np's) have an interesting surface chemistry and unique plasmonic properties. They are used in a wide variety of applications ranging from consumer products like socks, medical dressing, computer chips and it is also shown to have antimicrobial, anti bacterial activity and wound healing. Ag Np toxicity studies have been limited to date which needs to be critically addressed due to its wide applications. Mouse embryonic stem (MES) cells represent a unique cell population with the ability to undergo both self renewal and differentiation. They exhibit very stringent and tightly regulated mechanisms to circumvent DNA damage and stress response. We used 10 nm coated (polysaccharide) and uncoated Ag Np's to test its toxic effects on MES cells. MES cells and embryoid bodies (EB's) were treated with two concentrations of Ag Np's: 5 µg/ml and 50 ug/ml and exposed for 24, 48 and 72 hours. Increased cell death, ROS production and loss of mitochondrial membrane potential and alkaline phosphatase (AP) occur in a time and a concentration dependant manner. Due to increased cell death, there is a progressive increase in Annexin V (apoptosis) and Propidium Iodide (PI) staining (necrosis). Oct4 and Nanog undergo ubiquitination and dephosphorylation post-translational modifications in MES cells thereby altering gene expression of pluripotency factors and differentiation of EB's into all the three embryonic germ layers with specific growth factors were also inhibited after Ag Np exposure. Flow cytometry analysis revealed Ag Np's treated cells had altered cell cycle phases correlating with altered self renewal capacity. Our results suggest that Ag Np's effect MES cell self renewal, pluripotency and differentiation and serves as a perfect model system for studying toxicity induced by engineered Ag Np's. ABSTRACT 2: The reprogramming of fibroblasts to pluripotent stem cells and the direct conversion of fibroblasts to functional neurons has been successfully man (open full item for complete abstract)

Committee: Hong Yiling (Advisor); Shirley J. Wright (Committee Member); Mark G. Nielsen (Committee Member); Tsonis A. Panagiotis (Committee Member); Shawn M. Swavey (Committee Member) Subjects: Biology

Doctor of Philosophy, University of Toledo, 2020, Chemistry

Metal monolayer-protected clusters (MPCs) are an important new class of small metal nanoparticles with discrete sizes and unique properties that are eminently tunable, such that changing even a single atom can modify the properties in technologically significant ways. Controlling the synthesis of MPCs remains a challenge, however, since a fundamental understanding of the mechanisms of MPC formation is still lacking. Here, we begin the process of developing a detailed model of MPC synthesis by first establishing the basic mechanism by which silver-glutathione MPCs form. The molecularity of MPCs enabled real-time in situ optical measurements and ex situ solution-phase analyses of MPC populations present in the reaction mixture, which identified that MPCs grow systematically, increasing in size sequentially as they transform from one known species to another, in contrast to existing models. A new sequential growth model of MPC synthesis has been developed where the relative stability of each species in the series results in thermodynamic preferences for certain species as well as kinetic barriers to the transformation of one stable size to another. This model is shown to correctly predict the outcome of silver MPC synthetic reactions for the first time. Simple analytic expressions and simulations based on a series of rate equations were used to study the nature of the model and to validate it. The sequential growth model was able to provide new insights into how reactions may be directed, based on the interplay between the relative MPC stabilities and the reaction kinetics, to synthesize particular MPCs in high yield, providing new tools for MPC synthesis. While this newly proposed sequential growth mechanism successfully predicts the outcomes of synthetic reactions, it does not entirely explain all experimental observations. In particular, the evolution of MPC product sizes was found to be non-monotonic, first shifting to larger sizes with increasing reaction kinet (open full item for complete abstract)

Committee: Terry Bigioni (Committee Chair); Joseph Schmidt (Committee Member); Xiche Hu (Committee Member); Nikolas Podraza (Committee Member) Subjects: Chemistry; Materials Science; Nanoscience; Nanotechnology; Physical Chemistry

Doctor of Philosophy, University of Toledo, 2018, Chemistry

Noble metal nanoparticles have been extensively studied for use in applications in a diverse range of fields such as optoelectronics, catalysis, sensing, medicine, etc. due to their unique properties that arise as a result of their dimensions. Metal nanoparticles of size less than 3 nm exhibit molecular properties, unlike larger nanoparticles. These molecular nanoparticles are excellent model systems to study the chemistry of nanomaterials at the molecular level as their molecular formulae, crystal structure, chemical composition, electronic structures etc. can be experimentally measured and theoretically calculated. In addition, knowledge of their thermodynamic stability and mechanisms of formation can be leveraged in developing green synthetic routes in order to produce safer products that widen the range of applications, and to develop safer processes that increase manufacturability and decrease waste. Even though nanoparticle research is more focused on the end product and their properties, rather than the process, we have taken a different route of dismantling the M4Ag44(p-MBA)30 nanoparticle synthesis and developing a green route with significantly improved efficiency and an 89% yield. The need of solvent, which contributed to 98% of the waste, was kept to a minimum by using a stoichiometric silver-thiolate polymer as a precursor to intimately mix the metal atoms and ligands, and by forming a paste using a small amount of liquid to promote mass transport. The process mass intensity (PMI), a green metric defined by material input over product output, was decreased by almost 18-fold compared to the solution-phase synthesis. Some toxic chemicals were also removed or replaced throughout the process. This method is very effective for thermodynamically favorable products, and should be useful for other systems too. Alloying of metal nanoparticles is advantageous to achieve new properties. For example, gold-silver bimetallic NPs can be more stable than silver (open full item for complete abstract)

Committee: Terry Bigioni (Committee Chair); Joseph A. R. Schmidt (Committee Member); Dragan Isailovic (Committee Member); Nikolas Podraza (Committee Member) Subjects: Chemistry

Doctor of Philosophy, University of Toledo, 2017, Chemistry

Small silver nanoparticles, also called molecular nanoparticles (MNPs) or nanoclusters, are of great research interest due to potential applications in valuable fields such as biomedicine and catalysis. In the past decade, several groups reported successful formulae determination and crystal structures of the various species in this class of materials. Knowing such information is of crucial importance to start testing how slight modifications of both metal core and ligand shell affect the stability and properties of molecular nanoparticles. Among the techniques employed for characterization of MNPs, mass spectrometry plays a vital role. Soft ionization techniques such as matrix-assisted laser desorption ionization (MALDI) and electrospray ionization (ESI), developed primarily for bioanalytical applications, became indispensable for the analysis of MNPs, most of which are labile during the ionization process. Mass spectrometry also provides the high precision required to measure the precise numbers of metal atoms, ligands and charges and thereby determine the formulae of these molecules. While modified samples often resemble a statistical distribution of a product mixture, individual products can be successfully discriminated by their mass using tandem mass spectrometry and singled out such that their behavior in the gas phase can be studied. The all-silver M4Ag44(p-MBA)30 cluster was used as a model system, where M is a monocationic counterion and p-MBA is para-mercaptobenzoic acid, which serves as a protecting ligand. Metal core modifications were carried out by substituting gold for silver to form M4AuxAg44-x(p-MBA)30 clusters. Gold was chosen as a second metal due to some of its properties being similar to those of silver, including its electronic structure and atomic size. Co-reduction and galvanic exchange were the two methods used for the preparation of the bimetallic product. The range of product composition was determined, and the most thermodynamically (open full item for complete abstract)

Committee: Terry Bigioni (Committee Chair); Cora Lind-Kovacs (Committee Member); Dragan Isailovic (Committee Member); Nikolas Podraza (Committee Member) Subjects: Analytical Chemistry; Chemistry; Materials Science; Physical Chemistry

Doctor of Philosophy, The Ohio State University, 2015, Integrated Biomedical Science Graduate Program

Nanoparticles are increasingly being incorporated into common consumer products, including in foods and food packaging, for their unique properties at the nanoscale. Food-grade silica and titania are used as anti-caking and whitening agents, respectively, and these particle size distributions are composed of approximately one-third nanoparticles. Zinc oxide and silver nanoparticles can be used for their antimicrobial properties. However, little is known about the interactions of nanoparticles in the body upon ingestion. This study was performed to investigate the role of nanoparticle characteristics including surface chemistry, dissolution, and material type on toxicity to the intestinal epithelium. Only mild acute toxicity of zinc oxide nanoparticles was observed after 24-hour treatment of intestinal epithelial C2BBe1 cells based on the results of toxicity assays measuring necrosis, apoptosis, membrane damage, and mitochondrial activity. Silica and titanium dioxide nanoparticles were not observed to be toxic although all nanoparticles were internalized by cells. In vitro digestion of nanoparticles in solutions representing the stomach and intestines prior to treatment of cells did not alter nanoparticle toxicity. Long-term repeated treatment of cells weekly for 24 hours with nanoparticles did not change nanoparticle cytotoxicity or the growth rate of the treated cell populations. Thus, silica, titanium dioxide, and zinc oxide nanoparticles were found to induce little toxicity in intestinal epithelial cells. Fluorescent silica nanoparticles were synthesized as a model for silica used in foods that could be tracked in vitro and in vivo. To maintain an exterior of pure silica, a silica shell was hydrolyzed around a core particle of quantum dots or a fluorescent dye electrostatically associated with a commercial silica particle. The quantum dots used were optimized from a previously reported microwave quantum dot synthesis to a quantum yield of 40%. Characteri (open full item for complete abstract)

Committee: W. James Waldman PhD (Advisor); Prabir Dutta PhD (Committee Chair); Narasimham Parinandi PhD (Committee Member); Estelle Cormet-Boyaka PhD (Committee Member) Subjects: Biomedical Research; Nanotechnology; Toxicology

MS, Kent State University, 2010, College of Arts and Sciences / Department of Chemistry

Soft-templating synthesis of mesoporous carbons in the presence of tetraethyl orthosilicate (TEOS) and metal salts was carried out to introduce nickel and separately silver nanoparticles and also create additional microporosity in these materials. This strategy was employed to synthesize phenolic resin-based mesoporous carbons with two different loadings of metallic nanoparticles and to obtain nickel-containing mesoporous carbon-silica hybrids and silver-containing mesoporous carbons. Removal of silica with NaOH solution from the hybrid nickel composites gave mesoporous carbons with Ni particles and comparatively removal of silica from mesorporous carbons with silver gave mesoporous carbons with Ag particles. Inversely, burn off of carbon from the aforementioned Ni hybrid composites gave NiO-containing mesoporous silicas. Nitrogen adsorption, small and wide angle X-ray diffraction, transmission electron microscopy and thermogravimetric analysis showed good adsorption and structural properties of the aforementioned materials.

Committee: Mietek Jaroniec (Committee Chair); Anatoly Khitrin (Committee Member); Songping Huang (Committee Member) Subjects: Materials Science

Master of Science, University of Akron, 2024, Polymer Science

Dental caries are caused by oral microbiota producing acid via sugar metabolism. Streptococcus mutans (S. mutans) is the predominant aerobic cariogenic pathogen within dental plaque, whereas Fusobacterium nucleatum (F. nucleatum) represents anaerobic bacteria associated with periodontal disease and some inflammatory diseases, including irritable bowel syndrome and rheumatoid arthritis. Bacteria may develop antimicrobial resistance to traditional antibiotics and Ag NPs but not Silver-doped hydroxyapatite nanoparticles (AgHAP NPs), making the latter an attractive biocompatible material for dental applications. The Sahai group's previous studies showed (a) Ag content of AgHAP NPs depends on synthesis pH and (b) AgHAP NPs' antibacterial effects were shown by inhibition zone experiments but, in an apparent contradiction, relatively high MIC values were obtained for anaerobic bacteria F. nucleatum. The goals of the present study were to determine the antibacterial effects of AgHAP NPs with different synthesis pHs (pH7.5, 8, 8.5) on aerobic S. mutans and anaerobic F. nucleatum and to determine why MIC values were unexpectedly high for anaerobic strain F. nucleatum. Antimicrobial tests (MIC, inhibition zone, SEM visualization) showed antibacterial activity of AgHAP NPs which was related to Ag content and Ag+ release from NPs. Ionic conductivity measurements for Ag+ solutions with or without L-Cysteine under anaerobic and aerobic conditions were conducted, showing a dramatic drop in conductivity value only with the presence of L-Cysteine. Accepting the hypothesis that Ag+-thiol complexation reduces the availability of the toxic agent (Ag+) in the growth medium of F. nucleatum, which requires L-Cysteine to maintain anaerobic conditions. Thus, MIC values obtained were spuriously high, while inhibition zone results showed the true efficacy of AgHAP NPs against F. nucleatum.

Committee: Nita Sahai (Advisor); Ali Dhinojwala (Committee Member) Subjects: Biochemistry; Chemistry; Dentistry; Materials Science

Doctor of Philosophy (PhD), Wright State University, 2022, Environmental Sciences PhD

With the advent of nanotechnology, the potential applications of nanoscale gold in medicine have expanded substantially. Gold's therapeutic and toxic properties have been widely studied; however, little is known regarding gold's contribution to oxidative stress in red blood cells (RBCs). This is especially true for recently designed large (L) gold nanorods (GNRs), which possess unmatched theranostic capabilities. Here, we report on the effect of LGNRs at the level of cellular function, and particularly on ion transport and the glutathione (GSH) concentration in human (H) RBCs. Gold has been hypothesized to effectively react with RBCs sulfhydryl groups, thereby causing depletion of the antioxidant reserve represented by GSH and its pathway, through which GNRs induced cellular toxicity. The present study examined the effect of LGNRs on Rb+ and K+ metabolism and the GSH concentration in cord and adult human RBCs (HRBCs). In conclusion, the unique properties of LGNRs could be further enhanced in a precision medicine setting. Multiple regulatory agencies, including the U.S. National Institute for Occupational Safety and Health (NIOSH) and the U.S. Environmental Protection Agency (EPA), have outlined the need to improve the risk assessment and control associated with the heavy use of nanomaterial-based consumer products. The Nanotechnology Product Database indicates that silver nanoparticles (AgNPs) are the main component of ~ 70% of the reported biomedical products. This work addresses this knowledge gap by combining CytoViva and Raman hyperspectral imaging to study the uptake, distribution, and toxicity of silver nanoparticles in human red blood cells (RBCs). To achieve this, RBCs in 5% glucose solution were incubated at 37 °C, for 60 min, with 150 µg mL-1 of negatively charged, spherical AgNPs of an average diameter of ~ 16 nm. These citrate-capped AgNPs were selected as a nano-model due to their wide use, biocompatible capping agent, low cost, and simple fabrication. (open full item for complete abstract)

Committee: Ioana E. Pavel Ph.D. (Committee Chair); Norma C. Adragna Ph.D. (Committee Co-Chair); Sushil R. Kanel Ph.D. (Committee Member); Ji Chen Bihl M.D., Ph.D. (Committee Member); Steven R. Higgins Ph.D. (Committee Member) Subjects: Environmental Science

Master of Science (MS), Wright State University, 2021, Chemistry

Nanomaterials have attracted significant attention in the last decade, with applications in everyday products. Amongst all known nanomaterials in use, silver is the leading metal, present in 531 different types of products, owing to their unique optical, electrical, antimicrobial, and thermal properties. Though silver nanoparticles (AgNPs) come in contact regularly with the general population, there is little known about their toxicity mechanism due to limited techniques for thorough analysis. CytoViva Hyperspectral Imaging (HSI) shows potential for filling these gaps. In this study, borohydride-capped AgNPs with an approximate diameter of 10 nm were synthesized using the modified Creighton method and characterized by Raman spectroscopy, inductively coupled plasma optical emission spectroscopy (ICP-OES), ultraviolet-visible absorption spectroscopy (UV-Vis), and CytoViva HSI. Vero 76 cells were then incubated for 2 hr with 0.0, 0.1, and 3.0 mg L-1 Ag+ and 3.0 mg L-1 borohydride-capped AgNPs and compared to control Vero 76 cells via CytoViva HSI. The hyperspectral signatures were deconvoluted utilizing peak centers of cholesterol, cytochrome c, and phospholipids determined though a Voigt fit. Visually, the 3.0 mg L-1 Ag+ and AgNP exposures displayed cell degradation through the presence of cell debris and change in cell shape. Additionally, t-tests performed on the deconvoluted peaks showed statistical significance in Ag+ and AgNP groups, especially with the peak associated with cytochrome c, indicating mitochondrial interaction.

Committee: Ioana Pavel Ph.D. (Advisor); David Dolson Ph.D. (Committee Member); Steven Higgins Ph.D. (Committee Member) Subjects: Chemistry

Master of Science (MS), Wright State University, 2019, Chemistry

A fourth of the world's population lack access to safe water, thus the need for a more effective water treatment is imperative. Interest in silver nanoparticles (AgNPs) has grown in the last decade. Unlike chlorine, AgNPs do not form disinfection by products (DBPs), making them a prime candidate for drinking water treatment. The main aim of this study was to compare the antibacterial activity of electrochemical silver nanoparticles (eAgNPs-f) of ~5 nm in diameter against well-established pathogens: Escherichia coli (E. coli), Klebsiella variicola (K. variicola), and Pseudomonas aeruginosa (P. aeruginosa) to chlorine and Ag+ for drinking water. This was achieved by determining the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of eAgNPs, which were synthesized electrochemically and then concentrated (eAgNPs-f). The MIC values for E. coli, K. variicola, and P. aeruginosa were 4 ± 3, 3 ± 2, and 3 ± 2 mg/L, respectively. The MBC values for the same bacteria were 4 ± 3, 5 ± 2, and 5 ± 4 mg/L, respectively. When tested against chlorine, the MIC and MBC values increased over 1000-fold. CytoViva Hyperspectral Microscopy demonstrated the eAgNPs-f's affinity for the cellular membrane of E. coli after 30 minutes and physical cellular damage after 1 hour. Membrane disruption was confirmed through monitoring K+ leakage on ICP-OES. It was found that eAgNPs-f have a rapid and time consistent effect on K+ leakage, when compared to untreated control cells and Ag+. These results suggest that eAgNPs-f containing Ag+ ions are a more effective antibacterial agent than Ag+ alone, or chlorine.

Committee: Ioana E. Pavel Ph.D. (Advisor); David A. Dolson Ph.D. (Committee Member); Steven R. Higgins Ph.D. (Committee Member); Marjorie M. Markopoulos Ph.D. (Committee Member) Subjects: Chemistry; Nanotechnology

PhD, University of Cincinnati, 2019, Engineering and Applied Science: Environmental Engineering

Nanotechnology is one of the most prospective technologies of this century and promises groundbreaking innovation in many fields due to the unique physicochemical characteristics of engineered nanomaterials (ENMs). The potential impacts of ENMs on aquatic environments and humans currently receive significant attention by both regulators and academia. Currently, approximately a quarter of all nano-enabled consumer products (CPs) contain silver nanoparticles (AgNPs). AgNPs are incorporated into a wide range of CPs (e. g., textiles, disinfectants, household appliances, industrial, medical, and scientific applications). The increased application of AgNPs will inevitably lead to their release into environmental systems. Therefore, the investigation and quantification of AgNPs in environmental matrices becomes critical to answer questions regarding their fate/transport and potential risks to the environment and human health. This dissertation aims to systematically explore the release of AgNPs in various environmental media. Also, this research work will aid in developing a rapid and sensitive approach for quantification of AgNPs-CPs in various matrices. First, the silver-containing nanoparticles were characterized in 22 consumer products that advertised the use of silver or colloidal silver as the active ingredient. A high degree of variability between measured and claimed values for total silver was detected. Primary silver particle size distributions by transmission electron microscopy showed two categories of particles - smaller particles (<5 nm) and larger particles (20-40 nm). This characterization study helps us to understand the potential human exposure risks posed by these CPs. Second, the dissolution trends of colloidal AgNPs in five products were investigated in deionized and tap water. These five CPs were selected from the characterization study. To expand our understanding on the fundamental mechanisms of dissolution of AgNPs in CPs, the dissolution beh (open full item for complete abstract)

Committee: Dionysios Dionysiou Ph.D. (Committee Chair); Souhail Al-Abed Ph.D. (Committee Member); Margaret Kupferle Ph.D. (Committee Member); Phillip M. Potter Ph.D. (Committee Member); George Sorial Ph.D. (Committee Member) Subjects: Environmental Engineering

Master of Science (MS), Wright State University, 2018, Chemistry

The production and incorporation of silver nanoparticles into consumer products and biomedical technologies has skyrocketed in recent years. Thus, it is vital that the uptake, distribution and molecular interaction of silver nanoparticles (AgNPs) with red blood cells is well studied. In this experiment, citrate capped AgNPs 5-10 nm in diameter were incubated with washed red blood cells in a 5% glucose solution for one hour. Unbound AgNPs were removed via glucose washes prior to quantification with graphite furnace atomic absorption spectroscopy and analysis via Cytoviva hyperspectral microscopy and Raman spectroscopy. It was determined that a high percentage of 48±5% of AgNPs were taken up by the cells. Approximately 70% of the AgNPs taken up were adhered to the cell membrane and the rest were found within the cells. Obvious membrane damage was observed in many of these cells. Hyperspectral data showed interaction of extracellular and intracellular AgNPs with cholesterol, phospholipids or other cell membrane components, and hemoglobin respectively. The intracellular interaction with hemoglobin was confirmed by the enhancement of characteristic hemoglobin Raman shifts. Diminished oxyhemoglobin peaks and enhanced deoxyhemoglobin peaks revealed that the AgNP exposed cells showed a decrease in oxygen binding which could have been a result of intracellular and/or extracellular AgNP interactions. After 24 hours of storage at 4°C, SERS enhancement of >400% proved extracellular AgNPs aggregated forming large clusters of cells. In addition to the proven toxicity of silver ions, the adverse effects seen in the results of this study show that exposure of AgNPs to the circulatory system could pose serious health concerns.

Committee: Ioana Pavel Ph.D. (Advisor); David Dolson Ph.D. (Committee Member); Norma Adragna Ph.D. (Committee Member) Subjects: Chemistry

Master of Science (MS), Wright State University, 2018, Pharmacology and Toxicology

Platelet Activating Factor (PAF) and its associated receptor, the PAF Receptor (PAFR), are important mediators of intercellular communication during an immune response. Once a physiological stimulus triggers an inflammatory response, epithelial, endothelial and immune cells synthesize and release PAF. PAF mediates the recruitment of immune cells, platelets, angiogenesis, expression of various genes, and increased PAF biosynthesis (Brown, 2006; Han, 2006; Whatley, 1988; Axelrod, 1988). In this study, we utilized HaCaT cells and a well characterized KB cell line derived from nasopharyngeal cells, which do not natively express the PAFR. KB cells had previously been transfected with a PAF receptor (KBP) or a mock transfection (KBM), yielding two cell lines. The KBM and KBP cell lines allow for a mechanistic in vitro assessment of charge-dependent nanoparticle (NP) mediated PAFR activation, where KBP cells should show more robust Interleukin-8 (IL-8) secretion than KBM cells. Furthermore, this cell model serves to identify PAFR agonist formation, which has been reported to be generated from cigarette smoke, ultraviolet B radiation, jet fuel, and other stimuli that result in oxidative stress. The PAFR is involved in clathrin-mediated endocytosis, yet the PAFR role in NP uptake has not been investigated. The ability of NPs to generate PAF agonists is not known and the mechanisms by which they are internalized have yet to be fully understood. To investigate whether NP charge contributes to direct PAF-like lipid formation, KBM, KBP and HaCaT cell lines were exposed to 1 to 100µg/mL of 40nm Ag-NPs that were functionalized with either branched polyethyleneimine (BPEI) or citrate to give them a positive or negative surface charge, respectively. We demonstrated; a charge-dependent increase in NP-induced IL-8 production in KBP and HaCaT cells; indirectly measured an increased activation of the PAFR after 24 hours of exposure in KBP and HaCaT cells; dose-dependent uptake of NPs in (open full item for complete abstract)

Committee: Saber Hussain Ph.D. (Advisor); Richard Salisbury Ph.D. (Committee Member); Mark Nelson Ph.D. (Committee Member); Terry Oroszi Ed.D. (Committee Member); Jeffrey Travers M.D., Ph.D. (Committee Member) Subjects: Biology; Nanoscience; Nanotechnology; Toxicology

Master of Science (MS), Wright State University, 2018, Chemistry

The emerging world of nanotechnology has been of great interest within the last few decades. In this regard, nanomaterials have since been implemented in a number of commercial applications including: aerospace technology, coatings, sensors, and biomedical technology. This work aimed to elucidate upon the applications of transition metal nanomaterials in two separate experimental studies. The first of these studies involved the investigation of two-dimensional molybdenum disulfide (MoS2) nanoparticles, and their role in the toughening mechanism of epoxy composites. Two separate exfoliation techniques were implanted to target the influence surface chemistry of the nanomaterial and solvent quality had on the bulk thermal, mechanical and chemical properties of the nanocomposite system. A suite of characterization tools including UV-Vis spectrophotometry, differential scanning calorimetry, thermal gravimetric analysis, dynamic mechanical analysis, FT-IR spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and atomic force microscopy (AFM) were executed to provide detailed information regarding property changes. In addition, a method was developed to monitor the nanoscale fracture mechanics of MoS2-epoxy nanocomposites using micro-tensile testing and SEM upon altered films. Results concluded that surface functionality of MoS2 within the studied models played a significant role in the toughening mechanism of epoxy composites. In addition, it was found that solvent quality greatly contributes to the curing behavior, as well as the chemical network formation of the material system. The second study involved a systematic investigation of the toxicity mechanism behind positively charged cetyltrimethyl ammonium bromide (CTAB)-capped silver nanoparticles (AgNPs) in Sprague-Dawley rats. To fully assess the toxic effects within the studied specimens, CTAB-capped AgNPs, as well as Ag+ and CTAB solutions were orally administered to experiment (open full item for complete abstract)

Committee: Ioana Pavel Ph.D. (Advisor); Steven Higgins Ph.D. (Committee Member); Dhriti Nepal Ph.D. (Committee Member) Subjects: Chemistry

Doctor of Philosophy, University of Akron, 0, Chemistry

Presently in the United States, cancer is the second leading cause of death for both men and women, with lung cancer attributing to approximately 28% of all cancer related deaths. Lung cancer can further be separated into two categories: small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC). Treatment of NSCLC will depend on the stage of the cancer and can include surgery, chemotherapy, and/or radiation therapy. Chemotherapy often involves a mixture of organic-based and heavy metal-based drugs. The downside of these drugs are that they usually have a narrow therapeutic index and can have detrimental side effects. Due to these downsides, there is a continuous need to develop new anti-tumor agents that have a wider therapeutic index to reduce devastating side effects on the patient while having the desired effect on the tumor cell. Recently, the Youngs group had developed silver N-heterocyclic carbene complexes that show in vitro anticancer properties against NSCLC cell lines, however, solubility of the drugs is an issue. This dissertation describes encapsulating these complexes into biodegradable nanoparticles, in vitro and in vivo testing of the nanoparticles as well as various compounds against a panel of cancerous cell lines. Chapter I goes into the background of medicinal N-heterocyclic carbene complexes and the background of various nanoparticles used for drug delivery as well as the fabrication of the nanoparticle. Chapter II discusses the synthesis of the biodegradable nanoparticles made from poly(D,L-lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) nanoparticles, encapsulation of the complexes, and use of various targeting moieties decorating the nanoparticle surface. In vitro testing for antimicrobial and anticancer properties are also reported. Chapter III aims to optimize silver N-heterocyclic carbene complexes into PLGA-PEG nanoparticles and studies the antimicrobial activities of these systems. Chapter IV shows t (open full item for complete abstract)

Committee: Wiley J. Youngs Dr. (Advisor); Claire A. Tessier Dr. (Committee Member); Peter L. Rinaldi Dr. (Committee Member); Sailaja Paruchuri Dr. (Committee Member); Yang H. Yun Dr. (Committee Member) Subjects: Biomedical Research; Chemistry; Medicine; Nanotechnology; Pharmaceuticals; Polymers

Master of Science (MS), Wright State University, 2018, Chemistry

With the ubiquitous burst of nanotechnology, silver nanoparticles (AgNPs) have become indispensable in numerous industrial, medicinal, and research applications. Consequently, AgNPs have been alarmingly disposed into subsurface water increasing the risk of human and environmental exposure. While mechanisms of AgNP cytotoxicity have been reported, research studies on AgNP transport in subsurface water are needed, according to U.S. Environmental Protection Agency (EPA). The main goal of this study was to investigate the environmental fate and transport of widely-used Creighton colloidal AgNPs in a laboratory transport system simulating a porous, saturated groundwater aquifer. To achieve this, a large volume of AgNPs was synthesized, characterized using a suite of well-established analytical and microscopy techniques, and manipulated by tangential flow filtration. AgNPs and a conservative tracer, Cl- as a potassium chloride solution, were pulse-injected upward through a one-dimensional laboratory column (5 cm in depth, 2.5 cm diameter) at fixed pH, flow rate, and ionic strength, and pore volume. Breakthrough curves for AgNP transport were constructed using UV-Vis absorption, flame atomic absorption spectroscopy (FAAS) and inductively coupled plasma optical emission spectroscopy (ICP-OES). Smaller AgNPs (1-20 nm in diameter) were found to elute faster than larger AgNPs (1-100 nm in diameter). Flow rate and AgNP size were found to influence the sorption of AgNPs onto the media, as evidenced by the size and shape of the non-equilibrium breakthrough curves. Facilitated transport was attributed to moderate electrostatic repulsions between the negatively charged AgNPs and the polar glass beads. The transport of the AgNPs through the one dimensional laboratory system and the accurate ICP-OES-based quantification of nanosilver concentration in colloidal samples were translated into two novel laboratory experiment modules, which were successfully implemented into the Experiment (open full item for complete abstract)

Committee: Ioana Sizemore Ph.D. (Advisor); Rachel Aga Ph.D. (Committee Member); David Dolson Ph.D. (Committee Member); Mark Goltz Ph.D. (Committee Member); Sushil Kanel Ph.D. (Committee Member) Subjects: Chemistry; Environmental Management; Environmental Science; Environmental Studies; Nanoscience; Nanotechnology

Master of Science (MS), Wright State University, 2017, Chemistry

Two techniques of emerging importance were used to study different biochemical phenomena: the fate of silver nanoparticles in Vero 76 African green monkey kidney cell mitochondria, and the effect of pH on tautomer ratios using cellular automata. In the first area of research Vero 76 Africa green monkey kidney cells were incubated with silver nanoparticles (AgNP) and ionic silver (Ag+). After 24 hours the cell mitochondria were harvested, then processed with CPE-TFF and ICP-OES. The initial AgNP incubation formed 52.9% ± 15.5% AgNP and 29.9% ± 4.0% Ag+, while the ionic silver incubation formed 9.5% ± 0.9% AgNP and 60.6% ± 6.3% Ag+. In addition to this, relative proportions of tautomers in solutions of differing pH were examined using cellular automata. The rule-based, bottom-up design of cellular automata can cause complexity to arise as an emergent property rather than being a programmed variable. The tautomeric equilibrium of 9-anthrone, 9-anthrol, and their common ion was studied. pH values of 4, 7, and 10, along with the tautomeric equilibrium equation and Henderson-Hasselbalch equation, and accompanying pKE and pKa values were used to determine simulation parameters. At pH values of 4 or 7, 9-anthrone was found to comprise over 99% of the total population, while at pH 10 both 9-anthrone and the common anion (deprotonated 9-anthrol) contributed 49.8% of the total population. In all cases 9-anthrol contribution was so small as to be considered inconsequential. In all cases results were found to agree with those obtained from differential equations, with less time and derivation involved while accounting for such realities as stochasticity and a system of non-continuous components.

Committee: Ioana Sizemore Ph.D. (Advisor); Paul Seybold Ph.D. (Committee Member); David Dolson Ph.D. (Committee Member) Subjects: Chemistry