Targeting The Cd47/Calreticulin Axis In Triple Negative Breast Cancer Using Ha Grafted Chitosan Nanoparticles Loaded With Doxorubicin And Polygodial, Hadir M. Emara

Theses and Dissertations

Background: Triple-negative breast cancer (TNBC) is considered the most aggressive subtype of breast cancer. Although progress in cancer treatment has led to better results for different types of breast cancer, TNBC remains particularly challenging due to persistent resistance to both chemotherapy and immunotherapy. This resistance ultimately renders chemotherapy less effective and is frequently associated with substantial side effects. Immunosurveillance significantly impacts the onset of cancer, the rise of resistance to therapies, and the likelihood of tumor recurrence. In this immunomodulatory process, Cluster of Differentiation 47 (CD47) and Calreticulin (CALR) are two key regulators. CD47 expression is strongly linked to anti-phagocytic …

Absolute Quantification And Identification Of Rna From Rna-Lipid Nanoparticles Using High Resolution Mass Spectrometry, Jason C. Funderburk

Theses and Dissertations

RNA therapeutics are a rising drug category with potential use for a range of conditions encompassing infectious diseases to therapies for cancer, diseases, and genetic disorders. RNA-lipid nanoparticles (RNA-LNPs) are the prominent delivery method for these therapeutics approved products include mRNA vaccines and polyneuropathy treatments. The emergency use authorizations and orphan drug status of current RNA-LNP drugs has allowed approval without finalization of the regulatory analytical procedures for quality monitoring. The objective of the study was to develop an LC-MS assay to simultaneously measure identity and concentration of two therapeutically relevant intact RNA constructs extracted from RNA-LNPs to enhance quality …

Hafnium Oxide-Based Nanoheterostructures For Catalytic Radiosensitization And Enhanced X-Ray Radiotherapy, Marlen Dariela Calix Quezada

Theses and Dissertations

Orthovoltage X-ray beams are attractive for surface and intra-operative radiotherapy. Yet, their clinical utility is constrained by rapid attenuation and the limited dose that can be delivered without harming healthy tissue. High-Z hafnium oxide (HfO₂) nanoparticles can boost local energy deposition through the photoelectric effect, while catalytic surface defects accelerate water radiolysis. Harnessing both mechanisms in a single nano-heterostructure could enable potent radiosensitization at diagnostic-range energies.

This thesis develops and evaluates HfO₂-based nanoheterostructures, both bare and Au-decorated, as catalytic radiosensitizers.

Two types of HfO₂ were evaluated, one was synthesized following a specific route and the …

Synthesis Of Photocleavable Molecules For Neurological Applications, Nishal Madujith Egodawaththa Arachchilage Don

Theses and Dissertations

In recent biomedical research, the precise control of molecular dynamics through light activation has emerged as a powerful tool, particularly in the field of neurobiology. This approach involves the use of photocleavable cages or photoprotective groups (PPGs) that are chemically tethered to biologically active molecules such as neurotransmitters or calcium chelators. These cages remain inert until exposed to specific wavelengths of light, typically in the visible range, triggering the release of the active compound with high spatiotemporal precision.

For neurotransmitter systems, such as glutamate (Glu), which plays a critical role in synaptic transmission and memory formation, researchers have developed novel …

Investigations On V2o5 And Its Derivative Nanocomposites For Photocatalytic Textile Organic Dye Degradation, Jenifer A

Theses and Dissertations

In recent times, organic dyes from industrial sludge become one of the significant causes of water contamination due to their utility in textile and paper manufacturing industries. These organic dyes are highly toxic and carcinogenic. Fortunately, the photocatalytic degradation process is a practical tool for decomposing toxic organic matter in wastewater by utilizing light. The photodegradation process can be performed using semiconductor materials to purify wastewater. Thus, semiconductor photocatalysis is a desirable alternative technique for decolorizing various organic pollutants.

In this context, the present work reports the preparation and characterization of V2O5 nanocomposites by facile methods and tests them against …

Manufacturing Of Aligned Electrospun Nanofiber Yarns For Their Enhanced Mechanical And Piezoelectric Properties, Adaugo Mary-Frances Enuka

Theses and Dissertations

Electrospinning is a widely used technique for producing nanofibers with diverse applications. This method uses polymer solutions and strong electric fields to generate nano-sized fibers with unique properties. This study presents a novel manufacturing approach that enables the production of electrospun poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) nanofiber yarns using an automated parallel track system and an adjustable roll-to-roll collector. This research examines the impact of an automated post-drawing system on the polymer chain orientation, crystallinity, tensile strength, morphology, and piezoelectric properties of PVDF-HFP nanofiber yarn. The results reveal that the post-drawing process significantly improves molecular alignment, increases tensile strength, and enhances the …

Phosphomolybdic Acid-Doped Zeolitic Imidazolate Framework-8 Hybrid: Nanostructured Material With Synergistic Antibacterial Effect, Mariam Mohammad Abdelkhalek

Theses and Dissertations

Bacterial infections represent a major global health concern, causing millions of deaths and significant economic burdens. The development of nanostructured surfaces with antibacterial activity can revolutionize infection control practices. In this study, a hybrid material of Zeolitic imidazolate framework-8 (ZIF-8) doped with phosphomolybdic acid (PMA) was synthesized and characterized by FESEM, EDS, XRD, FTIR, and N2 sorption isotherm. The antibacterial activity against Escherichia coli as a model organism was tested by colony forming unit (CFU) reduction assay, minimum inhibitory concentration (MIC), and time-kill curve. PMA@ZIF-8 performance as an antibacterial agent was superior to its individual constituents, suggesting synergistic effect of …

Levofloxacin Incorporated Extracellular Matrix Nanoparticles For Pulmonary Cystic Fibrosis Infections, Raahi Patel

Theses and Dissertations

Cystic fibrosis (CF) is a progressive genetic disorder that affects around 40,000 people in the United States. CF is characterized by a mutation in the CFTR protein that causes dysregulated ion transport across epithelial cells, producing viscous mucus in the lung that increases bacterial invasion, causing persistent infections and subsequent inflammation. Pseudomonas aeruginosa and Staphylococcus aureus are two of the most common infections in CF patients that are resistant to antibiotics. One antibiotic approved to treat these infections is levofloxacin (LVX) that functions to inhibit bacterial replication, but can be further developed into tailorable particles. Nanoparticles are an emerging inhaled …

Nanoformulations Of Essential Oils Extracted From Pistacia Lentiscus And Boswellia Sacra And Investigation Of Their Anticancer, Antimicrobial, And Antioxidant Activities., Obaydah Abd Alkader Alabrahim

Theses and Dissertations

Essential oils (EOs) obtained from natural sources have shown promising biological and therapeutical properties such as anticancer, antimicrobial, and antioxidant activities, attributing to their high content of a variety of bioactive components. However, EOs’ therapeutic properties are limited by their low stability, poor bioavailability, high volatility, and low targeting ability. Therefore, the encapsulation and nanoformulation of EOs can maximize their therapeutical efficiency and physicochemical properties while overcoming their undesirable side effects and drawbacks. EOs extracted from the resins of Pistacia Lentiscus var. Chia (P.oil) and Boswellia Sacra (B.oil) are two promising EOs that have shown great therapeutic potential. P.oil was …

Atomistic Assessment Of Drug-Phospholipid Interactions Consequent To Cancer Treatment: A Study Of Anthracycline Cardiotoxicity, Yara Elsayed Ahmed

Theses and Dissertations

Despite being one of the most effective chemotherapeutic agents developed to date, Anthracyclines are notorious for their cardiotoxicity. Their clinical use is frequently limited both in dosage and in prescription due to the severe cardiac damage they cause. The mechanism of anthracycline-induced cardiotoxicity is not yet fully understood. However, it is hypothesized that interactions with the myocardial membrane play an important role in imparting cardiotoxicity. In this study, we use molecular dynamics simulations and density functional theory calculations to study the anthracycline drug molecules and the interactions that they have with the myocardial membrane. We construct a myocardial membrane model …

Formulation Of Encapsulated Nanoparticles Of Leek Extract As Antimicrobial And Anticancer Agent, Rawan Hassan Mohamed Elghanam

Theses and Dissertations

Leek extract (LEK) has broad therapeutic activity. However, plant extract use has many drawbacks, which could be resolved using nanocarriers. The purpose of this research work was to prepare chitosan nanoparticles (CS NPs) encapsulating LEK and investigate their antioxidant, antimicrobial, and anticancer activity. Gas chromatography-mass spectroscopy was used to determine the LEK components. The CS-LEK NPs were produced by tripolyphosphate (TPP) crosslinking with chitosan (CS) the ionic gelation methodology. The particle size was 331 nm, zeta potential (ZP) was 28.9 mv, polydispersity index (PDI) was 0.4, encapsulation efficiency (EE) was 65.6%, and loading capacity (LC) was 28.8 % of the …

Enhancing Vanadium Redox Battery Performance Using Tungsten-Bismuth-Based Oxide Nanostructures As Electrode Modifiers, Taher Al Najjar

Theses and Dissertations

Renewable energy power plants require high efficiency conversion and storage systems that can store high amounts of energy and can be integrated with the electrical grid. Vanadium redox flow batteries are very promising for this application. However, one major drawback of VRFBs is their low power density which means that right now they cannot replace non-renewable energy sources. Different carbon materials are used as electrodes in VRFBs and each carbon material affects the battery’s performance in a different way. Modification of these electrodes can increase the power density of the battery. Some metal oxides like tungsten oxide can enhance vanadium …

Modelling Physico-Chemical Properties Of Binary Nano-Alloys By Nano-Thermodynamics And Machine Learning, Luke David Geoffrion

Theses and Dissertations

Nanoscience and nanotechnology are some of the fastest growing fields of materials science that have given impact to several fields of science including biology, medicine, and catalysis. These applications take advantage of several properties of nanoscale materials that are present at sizes below 100 nm namely the increased surface to volume ratio. From a theoretical point of view, nanoscience research is dominated by Density Functional Theory and Molecular Dynamics. These techniques dominate for good reason, but are not without their own limitations due to their computational complexity which results in very long calculation time to complete on materials whose size …

Formulation Of Coffee Extract As Polymeric Nanoparticles And Studying Their Potential Biological Activities, Nouran Sharaf

Theses and Dissertations

Coffee extract was prepared and optimized (by solvent extraction) and subsequently entrapped into PLGA nanoparticles using single emulsion-solvent evaporation method (using Design Expert software). Dynamic Light Scattering, Scanning Electron Microscope, Fourier Transform-Infrared Spectroscopy and Folin Ciocalteau assay were used to characterize the NPs and to aid in selecting the optimum formulation conditions. The optimized NPs were in-vitro evaluated for their antimicrobial (by agar-well diffusion method), antioxidant (by DPPH assay) and anticancer (by MTT assay) activities. Finally, the release rate study was conducted for the NP sample showing the highly promising results.

The succeeded NP sample, in terms of the most …

Role Of Ataxia Telangiectasia Mutated In The Repair Of Magnetite Nanoparticles Induced Double Strand Breaks Associated With Heterochromatin, Mie Mohamed Mounir

Theses and Dissertations

Magnetite nanoparticles particulate matter pollution is escalating in large cities like New Mexico, Manchester city, Cairo, and New Delhi. Combustion derived Magnetite nanoparticles was found deposited in internal vital organs of deceased residents of urban areas. A great deal of research focused on the genotoxic and cytotoxic effects of Magnetite Nanoparticles (MNPs). In our work we focus on the mechanisms employed in DNA repair of higher chromatin structures. We employed the sensitive analysis of anti γ-H2AX to detect and monitor the repair of DSBs following exposure to MNPs. A 2- fold delay in the repair of heterochromatin associated DSBs in …

The Antioxidant And Antimicrobial Activities Of Cornsilk Extract Encapsulated In Polysaccharide Nanoparticles, Maryam Mady

Theses and Dissertations

Corn silk possess antibacterial and antioxidant activities due to its phenolic compounds but they are of low bioavailability that requires some innovative techniques to develop such active ingredients in a safe and less toxic manner. Accordingly, silk extract SE was encapsulated in chitosan nanoparticles CS NPs, which is a natural and abundant polymer derived from chitin. Among 15 experimental trials via design expert software, the optimum formula of SE x\CS NPs was prepared at 800 rpm, 5hrs. on magnetic stirrer, and by CS: TPP ratio was 2.5:1. Then SEM showed the majority of particles size diameter in the range of …

Overcoming Mechanisms Of Acquired And Innate Doxorubicin Resistance Using Nanomedicine And Tumor-Associated Macrophage Immunotherapy, Rashed M. Almuqbil

Theses and Dissertations

ABSTRACT

Overcoming Mechanisms of Acquired and Innate Doxorubicin Resistance Using Nanomedicine and Tumor-Associated Macrophage Immunotherapy

By Rashed M. Almuqbil, Pharm.D.

Director: Sandro R.P. da Rocha, PhD

Cancer is a leading cause of death worldwide. The available treatment for solid tumors may include surgery, radiotherapy, immunotherapy, and chemotherapy or a combination of all those regimens. Chemotherapy is widely used in the treatment of both lung cancers and breast cancer, including metastases, irrespective of type and stage. The poor rates of survival can be attributed to late diagnosis, and due to the development of acquired and innate chemoresistance. Lung tumors are intrinsically …

Single-Molecule Investigation Of I-Motif Folding And Dynamics In Bioinspired Dna Platforms, Anoja Megalathan

Theses and Dissertations

Although the canonical right-handed B-DNA is the predominant form of DNA in cells, DNA can adopt other secondary structures such as hairpins, G-quadruplexes (G4), and intercalated motifs (i-motif). These secondary structures are typically formed in the regions with repeat sequences. Among many secondary structures DNA can adopt, G-quadruplexes and i-motifs (tetraplex structures formed in the G-rich and C-rich sequences, respectively) caught significant research interest in recent years due to the prevalence of G-rich and C-rich sequences in the human genome. While G-quadruplexes are extensively studied, little is known about i-motifs – especially their formation and stability under cellular environments. For …

Copper Sulfide Manganese Nanoparticles For Multimodality Imaging And Therapy, Ali S. Gawi Ermi

Theses and Dissertations

Abstract

COPPER SULFIDE MANGANESE NANOPARTICLES FOR MULTIMODALITY IMAGING AND THERAPY

By Ali S. Gawi Ermi, MSc

Inorganic nanoparticles (NPs) are compatible with metal-based multi-modality molecular imaging and targeted therapy. Copper sulfide nanoparticles (CuS NPs) are attractive photoacoustic and photothermal agents and are amenable to incorporation of radionuclides and paramagnetic elements to facilitate image-guided therapy. The aim of this work is to develop manganese (Mn)- doped CuS NP, intrinsically radiolabeled with radionuclides such as (Zirconium-89 (⁸⁹Zr), Copper-64/67 (^64/67Cu) and Manganese-52/55 (^52/55Mn)). This novel approach combines Photoacoustic (PA), Positron emission tomography (PET), Single-photon emission computed tomography …

Dendrimer-Based Antibiotics For The Treatment Of Bacterial Biofilm In Cystic Fibrosis (Cf), Younan Ma

Theses and Dissertations

Pseudomonas aeruginosa (PA) is the predominant pathogen in chronic lung infections of cystic fibrosis (CF) patients. The most important mechanism of adaptation of PA to host defense and antibiotic treatment is the formation of biofilms within the mucus layer covering the lung bronchi. The effectiveness of antibiotics such as aminoglycosides is significantly attenuated by their limited penetration through thick mucus and embedded biofilm matrix in patients’ lung. Inhaled tobramycin (Tobra), which is the most commonly used antibiotics in the treatment of PA infections for CF patients, is usually found to be in very high concentration in patients’ lung, and yet …

Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence

Theses and Dissertations

Combining vibrating mesh nebulizers with additional new technologies leads to substantial improvements in pharmaceutical aerosol delivery to the lungs across therapeutic administration methods. In this dissertation, streamlined components, aerosol administration synchronization, and/or Excipient Enhanced Growth (EEG) technologies were utilized to develop and test several novel devices and aerosol delivery systems. The first focus of this work was to improve the poor delivery efficiency, e.g., 3.6% of nominal dose (Dugernier et al. 2017), of aerosolized medication administration to adult human subjects concurrent with high flow nasal cannula (HFNC) therapy, a form of continuous-flow non-invasive ventilation (NIV). The developed Low-Volume Mixer-Heater (LVMH) …

Live Cell Biomass Tracking For Basic, Translational, And Clinical Research, Graeme Murray

Theses and Dissertations

Single cell mass is tightly regulated throughout generations and the cell cycle, making it an important marker of cell health. Abnormal changes in cell size can be the first indication of dysfunction in response to environmental stimuli such as cytotoxic drugs. Described here is the further development of high-speed live cell interferometry (HSLCI) to concurrently measure the changes in single cell mass of thousands of cells over time. Critically, the high-throughput nature of HSLCI provides realistic pictures of tumor heterogeneity. This throughput enabled HSLCI to correctly predict in vivo carboplatin sensitivity of three triple negative breast cancer patient derived xenografts, …

Enhancing Chemosensitivity Of Lung Cancers By Manipulating The Tumor Microenvironment: Local Lung Delivery And Nanocarrier-Based Therapies, Hanming Zhang

Theses and Dissertations

Cancer is the second leading cause of death in United States causing an estimated six hundred thousand death in 2019. Among different types of cancer, lung cancer is the leading cause of cancer related death in both male and female. While targeted therapy and immunotherapy have shown promising clinical outcomes, currently there remain a significant proportion of patients who do not benefit from these strategies or who cannot tolerate them, making Pt based doublet chemotherapy still an indispensable component in almost all stages of treatment. However, partially due to the poor tumor distribution of small molecule drug, the development of …

Formulation And Validation Of Nanoparticle Controlled Delivery For Chemotherapeutic Drug Products, Shani L. Levit

Theses and Dissertations

Taxol, a formulation of paclitaxel (PTX), is one of the most widely used anticancer drugs, particularly for treating recurring ovarian carcinomas following surgery. Clinically, PTX is used in combination with other drugs such as lapatinib (LAP) to increase treatment efficacy. Delivering drug combinations with nanoparticles has the potential to improve chemotherapy outcomes. In this study, we use Flash NanoPrecipitation, a rapid, scalable process to encapsulate weakly hydrophobic drugs (logP in vitro. Encapsulating either PTX or LAP into nanoparticles increases drug potency. When PTX and LAP are co-loaded in the same nanoparticle, they have a synergistic effect that is greater than …

Exosomes As Systemic Mediators Of Nanotube Induced Neurotoxicity, Christopher G. Canal

Theses and Dissertations

Extra-pulmonary effects of nanoparticle inhalation have been well documented; however, mechanisms for conveying peripheral bioactivity remain elusive. Recent studies point to indirect molecular mediators shed into the circulation. Protein and lipid alternatives to cytokines or chemokines have been proposed, yet the diversity among responses suggests a broader assemblage of factors. Recently we have proposed proteolytic fragment peptides as an additional source of bioactivity, which interestingly were significantly associated with exosomal proteins after enrichment analysis. Here we tested whether modeled exposure to multi-walled carbon nanotubes (MWCNT) could alter the composition and bioactivity of circulating exosomes. Male C57BL/6 mice were exposed by …

Development Of Dexamethsone Sodium Phosphate Loaded Nanoparticles For Treating Corneal Allograft Rejection, Vineet R. Kulkarni

Theses and Dissertations

Corneas are the most commonly transplanted tissue worldwide, with approximately 80,000 transplantations performed in the United States in 2018 alone. Corneal transplantation is used to restore the vision due to opaque corneas in various diseases such as fungal keratitis, keratoconus, Fuchs’s dystrophy, corneal ulceration, traumatic injury, abrasions or scarring, inflammation, and infection. Corneal transplant surgery could involve replacing the entire cornea (penetrating keratoplasty) or selective replacement of the corneal layers (e.g. Descemet’s membrane endothelial keratoplasty and deep anterior lamellar keratoplasty). Immunologic graft rejection is one of the main causes of graft failure in these corneal transplantations. The 2-year rejection rate …

Synthesizing Galactose Modified Polymeric Nanoparticles For Biofilm Inhibition Of Pseudomonas Aeruginosa, Tyler R. Flockton

Theses and Dissertations

Treating patients with antibiotics is becoming harder with the increase in antibiotic resistance. This is due to the widespread antibiotic use in clinical and agricultural settings. With antibiotic resistance outpacing new drugs making it to the market, developing new options to treat bacterial infections is and will be important. We created sugar modified nanoparticles to inhibit the biofilm formation of Pseudomonas aeruginosa.

P. aeruginosa is a gram-negative opportunistic pathogen that infects its host that has a compromised immune system. This makes it one of the most significant bacterial infection in hospitals. P. aeruginosa uses biofilms as an attack mechanism …

Facile Fabrication Of Superhydrophobic And Superolephilic Materials For Effective Oil Absorbtion And Oil-Water Separation, Ali Tawfeeq Abdulhussein

Theses and Dissertations

Surfaces that have a water contact angle (WCA) above 150° and a negligible difference between the receding and advancing contact angles are superhydrophobic, meaning that a simple, minimal tilt will cause water droplets to roll off the surfaces. Superhydrophobic surfaces are found in nature and can possess several fascinating properties, including the ability to self-clean. A typical superhydrophobic surface has micro/nanostructure roughness and low surface energy, which combine to give it its unusual anti-wetting properties. Because of their unique capabilities, superhydrophobic surfaces have interested scientists in research and industry fields for years. In recent decades, researchers have developed a number …

Photochromic Thermochromic Nanocomposite, Syed M. Mustafa Akailvi

Theses and Dissertations

We have proposed a new nanocomposite consisting of F-127 polymer, AuNR and thermochromic dyes (TCD) which change color when they are heated above a tunable transition temperature. This nanocomposite has been demonstrated to show rapid, reversible and easily detectable color change at the timescales of ~60ms without degradation of any of its constituents which makes it a good candidate for in-vitro and in-vivo studies of thermal ablation treatment for cancer. This nanocomposite makes it possible to overcome one of the major shortcomings of photothermal therapy (PTT) and plasmonic photothermal therapy (PPTT) by allowing the detection of heating occurring during PPTT …

Multifunctional Nanosystems For Targeting And Treating Cancer Cells, Vijayalakshmi Dantuluri

Theses and Dissertations

In the United States, breast cancer is one of the most frequently occurring and deadly cancers. Though various therapies have seen success, they have numerous negative side effects. The incorporation of nanomaterials with anticancer drugs could help avoid these side effects and enhance the drugs’ effects. Nanomaterials have many properties, such as size, shape, structure, morphology, and surface features, that can be precisely tuned by altering their chemical composition. In this work, we explored the use of graphene and gold nanorods to enhance drug localization in and destruction of cancer cells by targeted delivery of the drugs doxorubicin (Dox) and …