Structural And Computational Studies Of The Sars-Cov-2 Spike Protein Binding Mechanisms With Nanobodies: From Structure And Dynamics To Avidity-Driven Nanobody Engineering, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Nanobodies provide important advantages over traditional antibodies, including their smaller size and robust biochemical properties such as high thermal stability, high solubility, and the ability to be bioengineered into novel multivalent, multi-specific, and high-affinity molecules, making them a class of emerging powerful therapies against SARS-CoV-2. Recent research efforts on the design, protein engineering, and structure-functional characterization of nanobodies and their binding with SARS-CoV-2 S proteins reflected a growing realization that nanobody combinations can exploit distinct binding epitopes and leverage the intrinsic plasticity of the conformational landscape for the SARS-CoV-2 S protein to produce efficient neutralizing and mutation resistant characteristics. Structural …

Lipid Based Nanoparticles As A Novel Treatment Modality For Hepatocellular Carcinoma: A Comprehensive Review On Targeting And Recent Advances, Khaled Mahmoud, Shady Swidan, Mohamed A. El-Nabarawi, Mahmoud H. Teaima

Pharmacy

Liver cancer is considered one of the deadliest diseases with one of the highest disease burdens worldwide. Among the different types of liver cancer, hepatocellular carcinoma is considered to be the most common type. Multiple conventional approaches are being used in treating hepatocellular carcinoma. Focusing on drug treatment, regular agents in conventional forms fail to achieve the intended clinical outcomes. In order to improve the treatment outcomes, utilizing nanoparticles—specifically lipid based nanoparticles—are considered to be one of the most promising approaches being set in motion. Multiple forms of lipid based nanoparticles exist including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, …

The Use Of Advanced Spectral Imaging To Reveal Nanoparticle Identity In Biological Samples, Qamar A. Alshammari, Rajasekharreddy Pala, Ayan K. Barui, Saud O. Alshammari, Andromeda M. Nauli, Nir Katzir, Ashraf M. Mohieldin, Surya M. Nauli

Pharmacy Faculty Articles and Research

Nanoparticles (NPs) have been used in drug delivery therapies, medical diagnostic strategies, and as current Covid-19 vaccine carriers. Many microscope-based imaging systems have been introduced to facilitate detection and visualization of NPs. Unfortunately, none can differentiate the core and the shell of NPs. Spectral imaging has been used to distinguish a drug molecule and its metabolite. We have recently integrated this technology to a resolution of 9 nm by using artificial intelligence-driven analyses. Such a resolution allowed us to collect many robust datapoints for each pixel of an image. Our analyses could recognize 45 spectral points within a pixel to …

Biomedical Applications Of Lanthanide Nanomaterials, For Imaging, Sensing And Therapy, Qize Zhang, Stephen O'Brien, Jan Grimm

Publications and Research

The application of nanomaterials made of rare earth elements within biomedical sciences continues to make significant progress. The rare earth elements, also called the lanthanides, play an essential role in modern life through materials and electronics. As we learn more about their utility, function, and underlying physics, we can contemplate extending their applications to biomedicine. This particularly applies to diagnosis and radiation therapy due to their relatively unique features, such as an ultra-wide Stokes shift in the luminescence, variable magnetism and potentially tunable properties, due to the library of lanthanides available and their multivalent oxidation state chemistry. The ability to …

Surface Engineering For Controlled Growth And Deposition Of Nanomaterials - Assembly And Design At The Nano-Microscale, David Fox

Electronic Theses and Dissertations, 2020-2023

Materials with nanoscale dimensions offer several important benefits over bulk materials (e.g. increased surface area, low-cost, deviation from bulk properties, etc.). Such materials are critical components for next-generation energy storage materials, optoelectronic devices, and catalyst systems. However, these materials are often processed in liquid media, and their diminutive structures are fragile in the presence of capillary forces. As such, preparing uniform and stable nanomaterial coatings is a significant challenge. Herein, we discuss an approach where the substrate itself is factored into the assembly and growth of these materials. First, nanoporous surfaces were utilized to achieve a uniform deposition of one-dimensional …

How Small Organic Osmolytes Modulate Actin Filament Assembly Kinetics And Mechanics, Pavlo Kravchuk

Electronic Theses and Dissertations, 2020-2023

Actin filament assembly and mechanics are crucial for muscle contraction, maintenance of cell structure, motility, and division. Actin filament assembly occurs in a crowded intracellular environment consisting of various types of molecules, including small organic molecules known as osmolytes. Ample evidence highlights the protective functions of osmolytes such as trimethylamine-N-oxide (TMAO), including their effects on protein stability and their ability to counteract cellular osmotic stress. Recently, TMAO has been shown to counteract the denaturing effects of urea on actin filament assembly based on bulk fluorescence assays. Yet, how TMAO affects individual actin filament assembly dynamics and mechanics is not well …

Biomolecular Corona Stability In Association With Plasma Cholesterol Level, Duong N. Trinh, Meda Radlinskaite, Jack Cheeseman, Gunther Kuhnle, Helen M.I. Osborn, Paula Meleady, Daniel I.R. Spencer, Marco P. Monopoli

Articles

Biomolecular corona is spontaneously formed on the surface of nanoparticles (NPs) when they are in contact with biological fluids. It plays an important role in the colloidal stability of NPs, which is of importance for most of their medical applications and toxicity assessment. While typical studies use either blood plasma or serum from a pooled biobank, it is unclear whether differences in the media, such as cholesterol level or protein concentration, might affect the NP colloidal stability and corona composition. In this study, the silica corona was prepared at particularly low plasma concentrations (3%, v/v–1.98 mg/mL) to identify the critical …

Bottom‐Up Versus Top‐Down Strategies For Morphology Control In Polymer‐Based Biomedical Materials, Alexander B. Cook, Tristan D. Clemons

Faculty Publications

The size and shape of polymer materials is becoming an increasingly important property in accessing new functions and applications of nano-/microparticles in many scientific fields. New synthetic methods have allowed unprecedented capability for the facile fabrication of anisotropic and shape-defined nanomaterials. Bottom-up approaches including: emulsion polymerization techniques, amphiphile self-assembly, and polymerization-induced self-assembly, can lead to polymer particles with precise dimensions in the nanoscale. Top-down methods such as lithographic templating, and 3D printing, have increased the access to unique particle shapes. In this review, these recent developments are appraised and contrasted, with future research directions providing that focus on biomedical applications. …

Intracellular Trafficking And Distribution Of Cd And Inp Quantum Dots In Hela And Ml-1 Thyroid Cancer Cells, Min Zhang

Graduate Theses/Dissertations

The study of the interaction of engineered nanoparticles, including quantum dots (QDs), with cellular constituents and the kinetics of their localization and transport, has provided new insights into their biological consequences in cancers and for the development of effective cancer therapies. The present study aims to elucidate the toxicity and intracellular transport kinetics of CdSe/ZnS and InP/ZnS QDs in late-stage ML-1 thyroid cancer using well-tested HeLa cells as a control. The XTT viability assay showed that ML-1 cells, and non-cancerous mouse fibroblast cells, exhibit no viability defect in response to these QDs, whereas HeLa cell viability decreases. These results suggest …

A Study Of Cobalt (Iii) Oxide Nanoparticle Delivery Of Sirna Molecules Directed Against Signaling Intermediates Of The P2y2 Receptor, Rachel Blair Stroud

Graduate Theses/Dissertations

G protein-coupled receptors are evolutionarily ubiquitous sensors of extracellular signals, propagating intracellular signal cascades through heterotrimeric G proteins. P2Y₂ receptors are GPCRs which are activated by extracellular nucleotides to mediate signaling cascades via Gαq coupling. Many GPCRs are subject to a common mechanism for signal termination involving phosphorylation of the C-terminal tail followed by β-arrestin binding and subsequent endocytic internalization of the complex. This effect has been described for the P2Y₂ R in the 1321N1 astrocytoma cell line, and UTP-induced activation and desensitization profiles have been previously defined. There is need to develop molecular vehicles for safe and …

Exploiting Modulation Of The Blood-Brain And Blood-Tumor Barrier Permeability By Translational Focused Ultrasound For Therapeutic Delivery To Cns Metastases, Tasneem A. Arsiwala

Graduate Theses, Dissertations, and Problem Reports (ETD)

Transcranial low-intensity focused ultrasound is a unique technology to modulate the integrity of tight endothelial junctions and transiently increase BBB/BTB permeability to enhance therapeutic delivery. Despite promising early studies, present literature lacks agreement on key experimental conditions, which restricts our knowledge and the technique's widespread translation. This dissertation first provides a critical review of the current gaps in knowledge regarding the universal use of LiFUS in preclinical and clinical use. We then identify key parameters for translational and predictable opening of the BBB using a 3T MRI coupled with a clinical device. Our investigation highlights that passive permeability of the …

Characterization Of Nanoparticles Using Inductively-Coupled Plasma Mass Spectrometry, Jabez D. Campbell

Graduate Theses/Dissertations

Nanomaterials are a relatively new class of materials that have many applications which span a wide host of fields from medical products to consumer products. The possible compositions and forms of nanomaterials are just as varied as the applications. Therefore, a versatile characterization method is needed for researchers and regulators alike to ensure nanomaterials are properly used. Single Particle Inductively Coupled Plasma Mass Spectrometry (SP-ICP-MS) is a functional method that could fill the characterization need in the nanomaterial research field. Using data from both SP-ICP-MS tests and data from literature established characterization methods, the viability of making SP-ICP-MS the standard …

Tumor-Targeted Ph-Sensitive Manganese Oxide Nanoparticle For Enhanced Detection Of Breast Cancer Using Mri, Celia Martinez De La Torre

Graduate Theses, Dissertations, and Problem Reports (ETD)

In the United States, approximately 287,850 new cases of invasive breast cancer will be diagnosed, and over 43,000 women will die because of it in 2022. Currently, mammography is the gold standard for breast cancer surveillance. Although this detection technique is relatively cheap and fast, it misses about 1 in 5 breast cancers in younger women with dense breast tissue, causing a delay in treatment. Compared to mammography, magnetic resonance imaging (MRI) has superior soft-tissue contrast that elucidates structural differences within soft tissue to detect more breast cancers. However, MRI still misses

NEMO particles were produced by synthesizing manganese oxide …

A Highly Conductive, Flexible, And 3d-Printable Carbon Nanotube-Elastomer Ink For Additive Bio-Manufacturing, Andy Shar, Phillip Glass, Daeha Joung Ph.D.

Undergraduate Research Posters

The synthesis of a highly conductive, flexible, 3D-printable, and biocompatible ink has been of great interest in the field of bio-based additive manufacturing. Various applications include ultra-sensitive, microscale tactile sensors, patient-customizable scaffolds for cardiac and nerve tissue regeneration, and flexible electrocardiogram (ECG) electrodes. Here, a novel elastomeric carbon nanocomposite is presented consisting of amino-functionalized carbon nanotubes (CNT-NH₂) homogenously dispersed in a one-part room-temperature vulcanizing (RTV) silicone matrix. The use of acetone as a swelling solvent aids in electrical percolation through the elastomer matrix. CNT-NH₂ ratios can be tuned to fit various needs; higher tensile strength is favored …

Comparison Of Free Versus Encapsulated Drugs On 3t3 Differentiation, Simon H. Friedrich, Gabriel Volpe

Undergraduate Research Posters

The scope of this project was to design, synthesize and test targeted nanoparticles containing hydrophobic and hydrophilic drugs that promote browning in adipose tissue. For hydrophilic drugs the use of liposomes and their hydrophilic core is more useful than the PLGA nanoparticles which have hydrophobic cores. The inhibition of the FOXO1 pathway and modulation of autophagy in adipose tissue can promote browning of white adipose tissue, or an energy burning state where excess energy is burned as heat instead of stored in the cell. If successful, these drugs would offer an alternative treatment for obesity where changes to the patient's …

Cathode Electron Sources For Cold Field Emission: Fabrication Methodology For Discretely Patterned High Aspect Ratio Silicon Nanotips, Austin Luke Rose

Graduate Research Theses & Dissertations

The development of high aspect ratio electron sources for use in Cold Field Emission (CFE) is an area of research interest with a wide range of potential applications from electron microscopy to CFE X-ray sources for computed tomography in the medical field. The development of cathode electron sources that are capable of electron emission at room temperature is attractive because of their ability to produce bright high current electron beams with less energy spread than their Thermionic or Schottky equivalents. These parameters are impacted by the sharpness of the emitter’s apex, creating the desire for high aspect ratio emitters. Additionally, …

Succinylated Polyethylenimine Gene Delivery Agents For Enhanced Transfection Efficacy, Md. Nasir Uddin

Theses and Dissertations--Chemistry

Gene therapy aims to treat patients by altering or controlling gene expression. Today, most clinical approaches are viral-based due to their inherent gene delivery activity. However, there is still a significant interest in nonviral alternatives for gene delivery, particularly synthetic lipids and polymers, that do not suffer the immunogenicity, high cost, or mutagenesis concerns of viral vectors. Polymeric vectors are of particular interest due to the ability to further tune the polymer properties through the incorporation of additional functional units such as targeting ligands or shielding domains. Polyethylenimine (PEI), a highly cationic polymer, is often considered a benchmark for polymer-based …

From Dna Logic Gates To Dna Nanorobots, Tatiana Molden

Electronic Theses and Dissertations, 2020-2023

Due to their biocompatibility and parallel data processing, DNA computational devices are highly desired for applications in diagnosis and treatment of cancer, infectious and genetic diseases. Much like in modern electronic devices, DNA computation is based on the logic gates - by directly interacting with DNA or RNA input molecules, they produce a specific output depending on their embedded logic function. This work is devoted to the development of functional parts of a future DNA nanorobot for biomedical applications. Specifically, we used DNA nanotechnology and the concept of multicomponent DNA probes to develop three parts of the DNA nanorobot: computing, …

Qbd Based Design And Characterization Of Proniosomal Transdermal Delivery Of Atenolol And Glibenclamide Combination: An Innovative Approach, P Anitha, S. Ramkanth, S. V. Satyanarayana

Bulletin of Faculty of Pharmacy Cairo University

There are numerous circumstances where chronic disease is associated with other disorders, especially in diseases like diabetes with noncommunicable disease risk factors, such as hypertension. This study shows a novel and innovative combinational proniosomal delivery of combination to beat the reactions by complex therapeutic regimen, and to improve patient compliance after controlling combinational transdermal delivery of Glibenclamide (GLB) and Atenolol (ATN) which have not been tried actually. To achieve the above reason, proniosomes were prepared and optimized utilizing Box-Behnken design. The ideal formulation was chosen by a point prediction method and formulation showed vesicle size of 562 ± 1.223 nm, …

Attenuating Effect Of Vitamin E Against Silver Nano Particles Toxicity In Submandibular Salivary Glands, Mahmoud Bakr, Mahmoud Al Ankily, Sara M. Shogaa, Mohamed Shamel

Dentistry

Open AccessArticle

Attenuating Effect of Vitamin E against Silver Nano Particles Toxicity in Submandibular Salivary Glands