Nanomedicine Commons^™

Theranostic Applications Of Sirna Bioconjugates In Cancer Detection And Treatment, Sunil S. Shah

Seton Hall University Dissertations and Theses (ETDs)

Abstract

The emerging field of RNA nanotechnology has led to rapid advances in the applications of RNA in chemical biology, medicinal chemistry, and biotechnology. At the forefront of its utility is the ability to self-assemble multiple siRNAs into nanostructure formulations capable of targeting selected oncogenes and potentiating the gene therapy of malignant tumors. Self-assembled siRNA integrates multiple siRNAs within a single molecular platform for silencing multiple oncogenic mRNA targets with high precision and efficacy to potentially induce cancer cell apoptosis through the RNA interference (RNAi) pathway. Furthermore, the conjugation of siRNA self-assemblies with bio-active probes results in multi-functional theranostic (therapy+diagnostic) …

Development Of Biomaterials For Drug Delivery, Raquel De Castro

Graduate Theses and Dissertations

Drug delivery systems (DDS) have highly evolved in the last decades with the development of hydrogels and nanoparticles. However, high systemic uptake, side effects, low bioavailability, and encapsulation efficiency continue to be a major hurdle faced by such DDSs.

Nanoparticles and hydrogels can be specifically designed for targeted DDSs to mitigate some of the problems. This dissertation aimed to design two DDSs for ocular drug delivery and one for cancer treatment. The first project sought to develop chitosan nanoparticles (Cs-NP) using PEGDA as a copolymer to encapsulate gentamicin (GtS) for ocular drug delivery. Cs-NPs contain positive charges that can interact …

Human Ace2‑Functionalized Gold “Virus‑Trap” Nanostructures For Accurate Capture Of Sars‑Cov‑2 And Single‑Virus Sers Detection, Yong Yang, Yusi Peng, Chenglong Lin, Li Long, Jingying Hu, Jun He, Hui Zeng, Zhengren Huang, Zhi-Yuan Li, Masaki Tanemura, Jianlin Shi, John R. Lombardi, Xiaoying Luo

Publications and Research

The current COVID-19 pandemic urges the extremely sensitive and prompt detection of SARS-CoV-2 virus. Here, we present a Human Angiotensin-converting-enzyme 2 (ACE2)-functionalized gold “virus traps” nanostructure as an extremely sensitive SERS biosensor, to selectively capture and rapidly detect S-protein expressed coronavirus, such as the current SARS-CoV-2 in the contaminated water, down to the single-virus level. Such a SERS sensor features extraordinary 106- fold virus enrichment originating from high-affinity of ACE2 with S protein as well as “virus-traps” composed of oblique gold nanoneedles, and 109- fold enhancement of Raman signals originating from multicomponent SERS effects. Furthermore, the identification standard of virus …

Remotely Controlled Enzyme Behavior Using Localized Thermal Gradients, Sarah Brown

UNO Student Research and Creative Activity Fair

No existing model describes an identified special case of enzyme behavior when directly stimulated with thermal energy via an RF field.

The ability to remotely influence cellular functions and outcomes is a new approach to targeted medicine. Nano-medicine and biotechnology are the future of medical diagnostics and treatment. The ability to remotely influence cellular functions and outcomes is a new approach to targeted medicine. Direct heating of an enzyme vs bulk heating changes the enzyme activity.

I tested how direct transfer of thermal energy changes rates of enzyme reactions. We created samples of enzymes, attached to ferrous (magnetic) nano-particles, and …

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, …

Design, Synthesis And Applications Of Nanoparticles In Suppression Of Mosquito-Born Flaviviridae Viruses, Maria R. Blahove

College of Graduate Studies: Theses & Dissertations

Recently, nanoparticles have become an origin of exploration in the chemistry field due to their unique medical uses. The current drug delivery models of nanoparticles often include a metal base with a drug conjugated to its surface. However this raises concerns regarding toxicity. A novel approach to solving this dilemma is the development of nanosized biocompatible polymer-based micelles, created from PEG-PCL-PEG triblock polymer, and formed around a drug of choice. The goal is to create a drug carrier nanoparticle system that is labile at a specific intracellular pH, without undue toxicity to the cell. This creates a drug-loaded nanoparticle that …

Silicon Quantum Dots Conjunctive With Stable Radicals: Potential Application In Non-Invasive Cancer Diagnostics, Daylan R. Post

Honors College Theses

Quantum Dots, and nanomaterials in general, are one of the most promising areas of current physical study, especially their potential medical uses. In this study we introduced Nitroxide free radicals into a Silicon Quantum Dot (SiQD) solution and conducted experiments on the modified SiQDs in order to characterize their physical properties. We gathered emission, excitation, absorption and electron spin resonance (ESR) spectra of both modified and unmodified SiQDs. Previous studies have shown the possibility of using proteins as markers for cancer detection. Our measurements show the potential of using the interaction between these protein markers and SiQDs as a form …

Interfacial Current Distribution Between Helium Plasma Jet And Water Solution, Sui Wang, Dingxin Liu, Zifeng Wang, Yifan Liu, Qiaosong Li, Xiaohua Wang, Michael G. Kong, Mingzhe Rong

Bioelectrics Publications

The plasma-liquid interaction holds great importance for a number of emerging applications such as plasma biomedicine, yet a main fundamental question remains about the nature of the physiochemical processes occurring at the plasma-liquid interface. In this paper, the interfacial current distribution between helium plasma jet and water solution was measured for the first time by means of the splitting electrode method, which was borrowed from the field of arc plasma. For a plasma plume in continuous mode, it was found that the mean absolute current distribution at the plasma-liquid interface typically had an annular shape. This shape could be affected …

Synthesis Of New Aliphatic Pseudo-Branched Polyester Co-Polymers For Biomedical Applications, Zachary Shaw

Electronic Theses & Dissertations

In this study, a hyperbranched polyester co-polymer was designed using a proprietary monomer and diethylene glycol or triethylene glycol as monomers. The synthesis was carried out using standard melt polymerization technique and catalyzed by p-Tolulenesulfonic acid. The progress of the reaction was monitored with respect to time and negative pressure, with samples being subjected to standard characterization protocols. The resulting polymers were purified using the solvent precipitation method and characterized using various chromatographic and spectroscopic methods including GPC, MALDI-TOF, and NMR. We have observed polymers with a molecular weight of 29,643 kDa and 33,996 kDa, which is ideal to be …

Therapeutic Delivery Technology And Its Economic Impact, Paul E. Savas Jr.

Senior Honors Theses

Therapeutic delivery technology is a current area of high interest in both university and industrial settings. These technologies are being developed in order to deliver therapeutic agents, such as genes, proteins, and drugs, to patients more efficiently. Nanoscale delivery vehicles have proven to be useful for these applications; these vehicles may either be naturally produced or chemically synthesized. The physical properties of these nanomaterials must be characterized correctly using instrumentation that evaluates their size, morphology, and potential for agglomeration. These technologies represent a high-growth economic area that fosters entrepreneurship and innovation. Because of this innovative spirit, research and economic interest …

Combination Therapy: Parp Inhibitor Synergizes The Therapeutic Efficacy Of Doxorubicin In The Treatment Of Prostate Cancer, Momin Ansare

Electronic Theses & Dissertations

Men are most susceptible to prostate cancer in the United States. The general treatment options include surgery, hormone therapy, chemotherapy, and radiation therapy. But in recent days, the nanoformulation have shown promising applications in overcoming the drawbacks of the currently available treatment options. To complement, we tried to enhance the capability of the nanoparticle formulation by loading them with a novel drug combination for the treatment of prostate cancer. Herein, we synthesized folate conjugated iron oxide nanoparticles encapsulated with doxorubicin and olaparib for imaging and targeted treatment of prostate cancer. Both drugs are approved by FDA for clinical cancer treatment. …

Evaluation Of Drug-Loaded Gold Nanoparticle Cytotoxicity As A Function Of Tumor Tissue Heterogeneity., Hunter Allan Miller

Electronic Theses and Dissertations

The inherent heterogeneity of tumor tissue presents a major challenge to nanoparticle-medicated drug delivery. This heterogeneity spans from the molecular to the cellular (cell types) and to the tissue (vasculature, extra-cellular matrix) scales. Here we employ computational modeling to evaluate therapeutic response as a function of vascular-induced tumor tissue heterogeneity. Using data with three-layered gold nanoparticles loaded with cisplatin, nanotherapy is simulated with different levels of tissue heterogeneity, and the treatment response is measured in terms of tumor regression. The results show that tumor vascular density non-trivially influences the nanoparticle uptake and washout, and the associated tissue response. The drug …

Hyperthermia As A Cancer Treatment- From Theory To Practice, Graham Fullerton

CMC Senior Theses

Using iron super-paramagnetic and ferromagnetic nanoparticles composed of Fe₃O₄ molecules, scientists analyze the effectiveness and practicality of this new treatment theory, hyperthermia. The problems of magnetic particle density, isothermal barriers/cellular cooling thresholds, and nanoparticle specific targeting are addressed in this review.

Iron magnetic nanoparticles were chosen due to their relatively low biological reactivates and lack of subsequent cellular toxicity. However, there are significant heating problems associated with these magnetic nanoparticles due to their relative size and short thermal time constants or thermal half-lives. Effectively, these aforementioned issues create a phenomenon where cancerous cells, surrounded by unheated healthy …

One-Pot Syntheses And Characterizations Of “Click-Able” Polyester Polymers For Potential Biomedical Applications, James F. Beach Ii

Electronic Theses & Dissertations

In this study, a synthetic polyester polymer was designed using polyethylene glycol, sorbitol, glutaric acid and 4-pentynoic acid as monomers. The synthesis was carried out using standard melt polymerization technique and catalyzed by Novozyme-435, an enzyme suitable for polyesterification of biocompatible compounds. The progress of the reaction was monitored with respect to time and vacuum exposure, with samples being subjected to standard characterization protocols. Polymers with high molecular weight and water solubility were chosen for further modification into folate-functionalized polymeric nanoparticles for targeted drug delivery to cancer cells. This was achieved by employing a solvent diffusion method, wherein the polymer …

Development Of Diverse Size And Shape Rna Nanoparticles And Investigation Of Their Physicochemical Properties For Optimized Drug Delivery, Daniel L. Jasinski

Theses and Dissertations--Pharmacy

RNA nanotechnology is an emerging field that holds great promise for advancing drug delivery and materials science. Recently, RNA nanoparticles have seen increased use as an in vivo delivery system. RNA was once thought to have little potential for in vivo use due to biological and thermodynamic stability issues. However, these issues have been solved by: (1) Finding of a thermodynamically stable three-way junction (3WJ) motif; (2) Chemical modifications to RNA confer enzymatic stability in vivo; and (3) the finding that RNA nanoparticles exhibit low immunogenicity in vivo.

In vivo biodistribution and pharmacokinetics are affected by the physicochemical …

Assembly Of Nucleic Acid-Based Nanoparticles By Gas-Liquid Segmented Flow Microfluidics, Matthew L. Capek, Ross Verheul, David H. Thompson

The Summer Undergraduate Research Fellowship (SURF) Symposium

The development of novel and efficient mixing methods is important for optimizing the efficiency of many biological and chemical processes. Tuning the physical and performance properties of nucleic acid-based nanoparticles is one such example known to be strongly affected by mixing efficiency. The characteristics of DNA nanoparticles (such as size, polydispersity, ζ-potential, and gel shift) are important to ensure their therapeutic potency, and new methods to optimize these characteristics are of significant importance to achieve the highest efficacy. In the present study, a simple segmented flow microfluidics system has been developed to augment mixing of pDNA/bPEI nanoparticles. This DNA and …

2016-01-A3dsrinp-Csc-Sta-Cmb-522-Bps-542, Raymond Pulver, Neal Buxton, Xiaodong Wang, John Lucci, Jean Yves Hervé, Lenore Martin

Bioinformatics Software Design Projects

Cholesterol is carried and transported through bloodstream by lipoproteins. There are two types of lipoproteins: low density lipoprotein, or LDL, and high density lipoprotein, or HDL. LDL cholesterol is considered “bad” cholesterol because it can form plaque and hard deposit leading to arteries clog and make them less flexible. Heart attack or stroke will happen if the hard deposit blocks a narrowed artery. HDL cholesterol helps to remove LDL from the artery back to the liver.

Traditionally, particle counts of LDL and HDL plays an important role to understanding and prediction of heart disease risk. But recently research suggested that …

Antiviral Peptide Nanocomplexes As Potential Therapeutics For The Treatment Of Infectious Diseases, Jinjin Zhang

Theses & Dissertations

Hepatitis C Virus (HCV) is recognized as a major burden in global public health, which can be further exacerbated by several cofactors such as human immunodeficiency virus (HIV). Currently, there is no vaccine for HCV. The emergence of potent and highly specific direct-acting antivirals (DAA) has marked a new era in HCV therapy, however, the remaining issues like affordability, genotype dependency, and potential resistance still necessitate the development of additional therapeutic approaches to be used instead or in combination with DAA.

Recently, the antiviral peptide C5A (in our studies designated as p1) and its cationic derivative p41 have been identified …

Synthesis, Surface Functionalization, And Biological Testing Of Iron Oxide Nanoparticles For Development As A Cancer Therapeutic, Stanley E. Gilliland Iii

Theses and Dissertations

Iron oxide nanoparticles are highly researched for their use in biomedical applications such as drug delivery, diagnosis, and therapy. The inherent biodegradable and biocompatible nanoparticle properties make them highly advantageous in nanomedicine. The magnetic properties of iron oxide nanoparticles make them promising candidates for magnetic fluid hyperthermia applications. Designing an efficient iron oxide nanoparticle for hyperthermia requires synthetic, surface functionalization, stability, and biological investigations. This research focused on the following three areas: optimizing synthesis conditions for maximum radiofrequency induced magnetic hyperthermia, designing a simple and modifiable surface functionalization method for specific or broad biological stability, and in vitro and in …

Folate Targeted Agents For Diagnostic And Therapeutic Uses, Mekeda Carr

All Capstone Projects

Folic acid has been frequently exploited for target therapies geared toward overexpressed folate receptors on malignant cells. The folic acid/folate-receptor high affinity interaction can be used to not only target but image cancer cells. Folate-linked nanoparticles represent a potential new drug carrier for tumor cell-selective therapeutics. Folate targeting, nanoparticles in therapeutics, and cancer cell imaging will be outlined in this literature report.

Modified Seed Growth Of Iron Oxide Nanoparticles In Benzyl Alcohol: Magnetic Nanoparticles For Radio Frequency Hyperthermia Treatment Of Cancer, Stanley E. Gilliland Iii

Theses and Dissertations

Iron oxide nanoparticles have received sustained interest for biomedical applications as synthetic approaches are continually developed for precise control of nanoparticle properties. This thesis presents an investigation of parameters in the benzyl alcohol synthesis of iron oxide nanoparticles. A modified seed growth method was designed for obtaining optimal nanoparticle properties for magnetic fluid hyperthermia. With a one or two addition process, iron oxide nanoparticles were produced with crystallite sizes ranging from 5-20 nm using only benzyl alcohol and iron precursor. The effects of reaction environment, temperature, concentration, and modified seed growth parameters were investigated to obtain precise control over properties …

Design And Fabrication Of Nanofluidic Systems With Integrated Sensing Electrodes For Rapid Biomolecule Characterization, Taylor Bradley Busch

Graduate Theses and Dissertations

A transparent nanofluidic system with embedded sensing electrodes was designed and fabricated by integrating Atomic Force Microscopy (AFM) nanolithography, Focused Ion Beam (FIB) milling and metal deposition, and standard microfabrication processing. The fabrication process started with the evaporation of chrome/gold (Cr/Au) onto a Pyrex 7740 wafer followed by photolithography and wet etching of the microchannels. The wafer was patterned a second time to form Au microelectrodes with 15-45 micrometer separation gaps in the nanochannel region. Sensing electrodes (up to one micron wide) were then deposited using FIB to bridge the gaps. The nanochannels were realized through both AFM nanolithography and …

Characterization Of Polymeric Phthalocyanine Nanoparticles Using Dynamic Light Scattering Laser, Satish Kumar Murarishetty

All Capstone Projects

The objective of this study is to use DLS (Dynamic Light Scattering) to analyze polymeric copper phthalocyanine nanoparticles (CuPcNPs). CuPcNPs are synthesized in order to facilitate drug penetration of bacterial biofilms for the treatment of chronic wounds. Microorganisms that reside inside the biofilms of chronic wounds are very resistant to any kind of treatment, even to the host’s own immune system. Therefore we have proposed an alternative method to destroy the microorganisms existing within the biofilms. Photodynamic anti-bacterial chemotherapy (PACT) has received much attention for the past decade due to the multi-drug resistant strands. PACT uses photons, a photosensitizer, and …

Nano Encapsulated Drug Delivery For Biofilms, Arunakanth Chavala

All Capstone Projects

Biofilms are now considered ubiquitous in the natural world. Bacterial biofilms have been observed to be extremely heterogeneous, both structurally and with regard to the physiology of the bacterial cells within them. The prevailing conceptual model depicts bacterial biofilms as being made up of microcolonies, which serve as the basic unit of the greater biofilm structure. A major concern with this approach is the frequently observed development of resistance to antimicrobial compounds. A number of elements in the process of biofilm formation have been studied as targets for novel drug delivery technologies. The present study aimed to penetrate biofilm by …

Nanoparticlated Drug Delivery System For Vitreous Humor, Kartheek K. Suragoni

All Capstone Projects

The purpose of this study is to develop a unique nanoparticulated system that has the capability of providing sustained drug delivery into the eyes. In ophthalmic preparations, poor ocular drug delivery of ocular dosage form is due to the production of tears and impermeability through corneal epithelium. The usage of liposomes in ophthalmic disorders shows promising results in ocular drug delivery. Liposomes are bilayered, microscopic vesicles surrounded by the aqueous compartments. Liposomes have the ability to encapsulate both hydrophilic and hydrophobic drugs. This unique property of liposomes helps in delivering the drug at specific site. This invention involves three major …

Using Photoactive Nanoparticles As Photodynamic Antimicrobial Chemotherapeutic (Pact) Agent To Treat Chronic Wounds, Chaitanya Poola

All Capstone Projects

The purpose of this study is to use photoactive vitamin nanoparticles as photodynamic antimicrobial chemotherapeutic agent to treat patients with chronic wounds. Chronic wounds are considered as a pandemic health problem which affects millions of people and increases ~10 % annually. According to the American Academy of Dermatology, the expense of treating chronic wounds constitutes over half of the total cost for all skin diseases. The main cause of chronic wounds is due to the existence of biofilms. Biofilms are complex microbial communities containing and are reported to be major factor contributing to multiple chronic inflammatory diseases. Owing to bacterial …

Detection Of Folate Binding Protein, Anwer Unnisa

All Capstone Projects

Cancer is the second leading cause of death despite the anti cancer developments including hormone therapy, radiotherapy, chemotherapy. Chemotherapy includes use of potent drugs such as camptothecin, paclitaxel and mitomycin. These drugs have an effect which is dose responsive, where the drug exposure and cell kill are proportional. This chemotherapy is high dose and has less selectivity for cancer cells and has more toxic effect to normal cells. Such kind of non specific treatment to tumor is causing hurdles in the treatment of cancer by chemotherapy. To overcome this current limitation to chemotherapy, the anti cancer drug with high specificity …

Using Photoactive Vitamin Nanoparticles As Photodynamic Antimicrobial Chemotherapeutic (Pact) Agents To Treat Chronic Wounds, Rahul A. Khanke

All Capstone Projects

The objective of the proposed study is to develop new materials and methods to manage microbial growth in chronic wounds using phototherapy. Chronic wounds are considered as a worldwide health problem. The most common chronic wounds can be classified into three categories: venous ulcers, diabetic ulcers, and pressure ulcers. Venous ulcers, which usually occur in the legs, account for about 70% to 90% of chronic wounds and can become infected easily. Venous ulcers are sores that develop after veins in the legs have been damaged. These ulcers can penetrate deeply into the skin. Occasionally, if a venous ulcer persists for …

Size-Controlled Synthesis Of Monodisperse Core/Shell Nanogels, William H. Blackburn, L. Andrew Lyon

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Small, monodisperse nanogels (similar to 50-nm radius) were synthesized by free-radical precipitation polymerization and were characterized using a suite of light scattering and chromatography methods. Nanogels were synthesized with either N-isopropylacrylamide or N-isopropylmethacrylamide as the main monomer, with acrylic acid or 4-acrylamidofluorescein as a comonomer and N,N'-methylenebis(acrylamide) as a cross-linker. By varying the surfactant and initiator concentrations, particle size was controlled while maintaining excellent monodispersity. An amine-containing shell was added to these core particles to facilitate subsequent bioconjugation. Successful conjugation of folic acid to the particles was demonstrated as an example of how such materials might be employed in a …