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Development Of New Biological Nanopores And Their Application For Biosensing And Disease Detection, Shaoying Wang 2016 University of Kentukcy

Development Of New Biological Nanopores And Their Application For Biosensing And Disease Detection, Shaoying Wang

Theses and Dissertations--Pharmacy

Nanopore technology has recently emerged as a new real-time single molecule sensing method. The current dominant technologies, such as mass spectrometry and immunoassay, for protein analysis is still slow and complex, which can’t meet the urgent need and fields of use. Development of a highly simple, portable and sensitive detection system for pathogen detection, disease diagnosis, and environmental monitoring is in great need. Membrane embedded Phi29 connector nanopore, the first protein nanopore coming from bacteriophage, was mainly focusing on DNA and RNA translocation in previous studies. Here, Phi29 connector nanopore was first time established for antibody detection by engineering Epithelial …


Rna Nanotechnology For Next Generation Targeted Drug Delivery, Fengmei Pi 2016 University of Kentucky

Rna Nanotechnology For Next Generation Targeted Drug Delivery, Fengmei Pi

Theses and Dissertations--Pharmacy

The emerging field of RNA nanotechnology is developing into a promising platform for therapeutically application. Utilizing the state-of-art RNA nanotechnology, RNA nanoparticles can be designed and constructed with controllable shape, size for both RNA therapeutics and chemical drug delivery. The high homogeneity in particle size and ease for RNA therapeutic module conjugation, made it feasible to explore versatile RNA nanoparticle designs for preclinical studies.

One vital module for therapeutic RNA nanoparticle design is RNA aptamer, which can enable the RNA nanoparticles find its specific target for targeted drug delivery. A system of screening divalent RNA aptamers for cancer cell targeting …


Rna As A Unique Polymer To Build Controllable Nanostructures For Nanomedicine And Nanotechnology, Hui Li 2016 University of Kentucky

Rna As A Unique Polymer To Build Controllable Nanostructures For Nanomedicine And Nanotechnology, Hui Li

Theses and Dissertations--Pharmacy

RNA nanotechnology is an emerging field that involves the design, construction and functionalization of nanostructures composed mainly of RNA for applications in biomedical and material sciences. RNA is a unique polymer with structural simplicity like DNA and functional diversity like proteins. A variety of RNA nanostructures have been reported with different geometrical structures and functionalities. This dissertation describes the design and construction of novel two-dimensional and three-dimensional self-assembled RNA nanostructures with applications in therapeutics delivery, cancer targeting and immunomodulation. Firstly, by using the ultra-stable pRNA three-way junction motif with controllable angles and arm lengths, tetrahedral architectures composed purely of RNA …


Structure-Activity Relationships Governing The Interaction Of Nanoparticles With Mammalian Cells – Predictive Models For Toxicology And Medical Applications., Marcus A. Maher 2016 Technological University Dublin

Structure-Activity Relationships Governing The Interaction Of Nanoparticles With Mammalian Cells – Predictive Models For Toxicology And Medical Applications., Marcus A. Maher

Doctoral

Nanoscience is seen as one of the key enabling technologies of the 20th century and as its range of applications increases it is important to look at how nanomaterials interact with biological environments. Some of these interactions have given rise to toxic effects and thus, the creation of the field of nanotoxicology, it has also been noted that current methods of evaluating toxicity may not be sufficient to keep up with the rapidly emerging range of nanomaterials becoming available. It is clear that alternatives are necessary. In this thesis, a phenomenological rate equation model is constructed to simulate nanoparticle uptake …


Understanding Dna Condensation By Low Generation (G0/G1) And Zwitterionic G4 Pamam Dendrimers, Min An 2016 University of Kentucky

Understanding Dna Condensation By Low Generation (G0/G1) And Zwitterionic G4 Pamam Dendrimers, Min An

Theses and Dissertations--Chemistry

Cationic polymers have shown potential as gene delivery vectors due to their ability to condense DNA and protect it from cellular and restriction nucleases. Dendrimers are hyperbranched macromolecules with precisely defined molecular weights and highly symmetric branches stemming from a central core. The nanosize, tunable surface chemistries and ease of surface functionalization has made dendrimers an attractive alternative to conventional linear polymers for DNA delivery applications. The commercially available, cationic dendrimer poly(amidoamine) or PAMAM is the most widely studied dendrimer for use as a gene delivery vector. The aim of this dissertation is to provide an increased understanding of the …


Biodegradable Hybrid Nanogels For Combination Chemotherapy, Swapnil Desale 2015 University of Nebraska Medical Center

Biodegradable Hybrid Nanogels For Combination Chemotherapy, Swapnil Desale

Theses & Dissertations

Combination chemotherapy is commonly used to treat cancer, because such a therapy regimens usually involve sequential administration of multiple drugs and allow targeting different cell signaling pathway. The co-delivery of drug combination at a controlled ratio via the same vehicle is offering the advantages such as spatial-temporal synchronization of drug exposure, synergistic therapeutic effects and suppression of drug resistance. Undoubtedly, there are several molecular and pharmacological factors that determine the effectiveness of drug combinations. A rationally designed drug combination is required since certain drug ratios and the definitive exposure to the targets of interest can only be synergistic while others …


Antiviral Peptide Nanocomplexes As Potential Therapeutics For The Treatment Of Infectious Diseases, Jinjin Zhang 2015 University of Nebraska Medical Center

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 …


Pamam Dendrimers As Promising Nanocarriers For Rnai Therapeutics, Prashant Kesharwani, Sanjeev Banerjee, Umesh Gupta, Mohd Cairul Iqbal Mohd Amin, Subhash Padhye, Fazlul H. Sarkar, Arun K. Iyer 2015 Wayne State University

Pamam Dendrimers As Promising Nanocarriers For Rnai Therapeutics, Prashant Kesharwani, Sanjeev Banerjee, Umesh Gupta, Mohd Cairul Iqbal Mohd Amin, Subhash Padhye, Fazlul H. Sarkar, Arun K. Iyer

Pharmaceutical Sciences Faculty Publications

Therapeutics based on RNA interference mechanisms are highly promising for the management of several diseases including multi-drug resistant cancers. However, effective delivery of siRNAs and oligonucleotides still remains challenging. In this regard, hyper-branched, PAMAM dendrimers having unique three-dimensional architecture and nanoscale size, with cationic surface charge can potentially serve as siRNA condensing agents as well as robust nano-vectors for targeted delivery. In addition, their surface functionality permits conjugation of drugs and genes or development of hybrid systems for combination therapy. Thus far, in vitro cellular testing of dendrimer-mediated siRNA delivery has revealed great potential, with reports on their in vivo …


When 1 + 1 > 2: Nanostructured Composites For Hard Tissue Engineering Applications, Vuk Uskoković 2015 Chapman University

When 1 + 1 > 2: Nanostructured Composites For Hard Tissue Engineering Applications, Vuk Uskoković

Pharmacy Faculty Articles and Research

Multicomponent, synergistic and multifunctional nanostructures have taken over the spotlight in the realm of biomedical nanotechnologies. The most prospective materials for bone regeneration today are almost exclusively composites comprising two or more components that compensate for the shortcomings of each one of them alone. This is quite natural in view of the fact that all hard tissues in the human body, except perhaps the tooth enamel, are composite nanostructures. This review article highlights some of the most prospective breakthroughs made in this research direction, with the hard tissues in main focus being those comprising bone, tooth cementum, dentin and enamel. …


Synthesis And Functional Evaluation Of Peptide Modified Poly (Lactic-Co-Glycolic Acid) Nanoparticles To Inhibit Porphyromonas Gingivalis Biofilm Formation., Paridhi Kalia 2015 University of Louisville

Synthesis And Functional Evaluation Of Peptide Modified Poly (Lactic-Co-Glycolic Acid) Nanoparticles To Inhibit Porphyromonas Gingivalis Biofilm Formation., Paridhi Kalia

Electronic Theses and Dissertations

Periodontal disease is an oral inflammatory disorder that afflicts roughly 46% of the adults in the U.S. Currently, treatment of periodontal disease involves the removal of plaque from the gingival pocket (with possible antibiotic treatment) and if necessary, gingival surgery. To our knowledge, no therapeutic approach exists that promotes host-biofilm homeostasis by limiting pathogen recolonization of the oral cavity after prophylaxis or treatment. The interaction of the pathogen Porphyromonas gingivalis with commensal streptococci is critical for initiation of periodontitis and represents a target for limiting P. gingivalis colonization of the oral cavity. Previous studies showed that a synthetic peptide …


Synthesis Of Graphitic Nanostructures On Noble Metals, Amelie Adele Parmentier 2015 University of Arkansas Little Rock

Synthesis Of Graphitic Nanostructures On Noble Metals, Amelie Adele Parmentier

Theses and Dissertations

In this research, two subjects are studied: the growth of graphene from various catalysts with RF-CVD and the growth of graphitic nanostructures from gold-decorated graphene with RF-CVD. In the first topic, various catalysts are made with magnesium oxide and metal nanoparticles: iron, silver and gold. Using a radio-frequency generator, these catalysts are heated and placed in contact with three gases (argon, hydrogen and methane). By controlling various parameters, graphene synthesis can happen. The results are analyzed with Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), Thermo-gravimetrical analysis (TGA), and X-ray diffraction (XRD). In the second topic, commercial graphene is functionalized …


Lipopolysaccharide Induced Map Kinase Activation In Raw 264.7 Cells Attenuated By Cerium Oxide Nanoparticles, Vellaisamy Selvaraj, Niraj Nepa, Steven Rogers, Nandini D.P.K. Manne, Ravi K. Arvapalli, Kevin M. Rice, Shinichi Asano, Erin Fankenhanel, J. Y. Ma, Tolou Shokuhfar, Mani Maheshwari, Eric R. Blough 2015 Marshall University

Lipopolysaccharide Induced Map Kinase Activation In Raw 264.7 Cells Attenuated By Cerium Oxide Nanoparticles, Vellaisamy Selvaraj, Niraj Nepa, Steven Rogers, Nandini D.P.K. Manne, Ravi K. Arvapalli, Kevin M. Rice, Shinichi Asano, Erin Fankenhanel, J. Y. Ma, Tolou Shokuhfar, Mani Maheshwari, Eric R. Blough

Pharmaceutical Science and Research

High mortality rates are associated with the life threatening disease of sepsis. Improvements in septic patient survivability have failed to materialize with currently available treatments. This article represents data regarding a study published in biomaterials (Vellaisamy et al., Biomaterials, 2015, in press). with the purpose of evaluating whether severe sepsis mortality and associated hepatic dysfunction induced by lipopolysaccharide (LPS) can be prevented by cerium oxide nanoparticles (CeO2NPs) treatment in male Sprague Dawley rats. Here we provide the information about the method and processing of raw data related to our study publish in Biomaterials and Data in Brief (Vellaisamy et al., …


Targeted Magnetite Tissue Delivery For Antiretroviral Pharmacokinetics, Tianyuzi Li 2015 University of Nebraska Medical Center

Targeted Magnetite Tissue Delivery For Antiretroviral Pharmacokinetics, Tianyuzi Li

Theses & Dissertations

Pharmacokinetics and pharmacodynamics studies are required for bench to bedside translation of any new drug, formulation or device. Multifunctional magnetite nanocarriers enable magnetic resonance imaging tracking of nanomaterial encased antiretroviral drugs serving to improve the effectiveness of formulation developments. Targeting ligands used to deliver nanoparticles to HIV harboring cells can be tested using multifunctional magnetite nanocarriers. To this end, two types of magnetite nanocarriers were developed. These included small magnetite antiretroviral therapy particles. The second were ALN-PEG coated magnetite particles for testing macrophages targeting ligands. Overall, these works should serve to speed the development of long acting nanoformulated ART to …


Polymeric Nanocarriers For Treatment Of Melanoma And Genetically Modified Mesenchymal Stem Cells To Improve Outcome Of Islet Transplantation, Vaibhav Mundra 2015 University of Nebraska Medical Center

Polymeric Nanocarriers For Treatment Of Melanoma And Genetically Modified Mesenchymal Stem Cells To Improve Outcome Of Islet Transplantation, Vaibhav Mundra

Theses & Dissertations

Melanoma is a lethal malignancy with limited treatment options for advanced metastatic stages. New targeted therapeutic options with discovery of BRAF and MEK inhibitors have shown significant survival benefit. Despite the recent progress, inefficient tumor accumulation and dose limiting systemic toxicity remains pressing challenges for treating metastatic melanoma and there is a need for drug delivery approach to improve therapeutic index of chemotherapeutics. Nanoparticle based drug delivery represents promising approach to enhance efficacy and reduce the dose limiting systemic toxicity. Nanoparticles can be formulated either by physical encapsulation of drugs or by covalent conjugation of drugs to the polymeric backbone. …


A Sensorless Haptic Interface For Robotic Minimally Invasive Surgery, Baoliang Zhao 2015 University of Nebraska-Lincoln

A Sensorless Haptic Interface For Robotic Minimally Invasive Surgery, Baoliang Zhao

Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research

Robotic minimally invasive surgery (R-MIS) has gained in popularity due to its advantages of improving the accuracy and dexterity of surgical interventions while minimizing trauma to the patient. However, because of the loss of direct contact with the surgical site, the surgeon cannot perceive tactile information, which may adversely affect surgical efficiency and/or efficacy. The lack of haptic feedback is regarded as a limiting factor in existing R-MIS technology.

To solve this problem, researchers have incorporated force sensors on the surgical tools to measure the tool-tissue interaction forces, and reproduce these forces at the surgeon console. However, the employment of …


15 Years On Sirna Delivery: Beyond The State-Of-The-Art On Inorganic Nanoparticles For Rnai Therapeutics, Joao Conde, Furong Tian, Alfredo Ambrosone, Yulán Hernandez, Mark McCully, Catherine C. .Berry, Pedro Baptista, Claudia Tortiglione, Jesus M. de la Fuented 2015 Universidad de Zaragoza, Spain

15 Years On Sirna Delivery: Beyond The State-Of-The-Art On Inorganic Nanoparticles For Rnai Therapeutics, Joao Conde, Furong Tian, Alfredo Ambrosone, Yulán Hernandez, Mark Mccully, Catherine C. .Berry, Pedro Baptista, Claudia Tortiglione, Jesus M. De La Fuented

Articles

RNAi has always captivated scientists due to its tremendous power to modulate the phenotype of living organisms. This natural and powerful biological mechanism can now be harnessed to downregulate specific gene expression in diseased cells, opening up endless opportunities. Since most of the conventional siRNA delivery methods are limited by a narrow therapeutic index and significant side and off-target effects, we are now in the dawn of a new age in gene therapy driven by nanotechnology vehicles for RNAi therapeutics. Here, we outlook the “do's and dont's” of the inorganic RNAi nanomaterials developed in the last 15 years and the …


New Approach To Develop Ultra-High Inhibitory Drug Using The Power Function Of The Stoichiometry Of The Targeted Nanomachine Or Biocomplex, Dan Shu, Fengmei Pi, Chi Wang, Peng Zhang, Peixuan Guo 2015 University of Kentucky

New Approach To Develop Ultra-High Inhibitory Drug Using The Power Function Of The Stoichiometry Of The Targeted Nanomachine Or Biocomplex, Dan Shu, Fengmei Pi, Chi Wang, Peng Zhang, Peixuan Guo

Pharmaceutical Sciences Faculty Publications

AIMS: To find methods for potent drug development by targeting to biocomplex with high copy number.

METHODS: Phi29 DNA packaging motor components with different stoichiometries were used as model to assay virion assembly with Yang Hui's Triangle [Formula: see text], where Z = stoichiometry, M = drugged subunits per biocomplex, p and q are the fraction of drugged and undrugged subunits in the population.

RESULTS: Inhibition efficiency follows a power function. When number of drugged subunits to block the function of the complex K = 1, the uninhibited biocomplex equals q(z), demonstrating the multiplicative effect of stoichiometry on inhibition with …


Bioresponsive Antisense Dna Gold Nanobeacons As A Hybrid In Vivo Theranostics Platform For The Inhibition Of Cancer Cells And Metastasis, Chenchen Bao, Joao Conde, James Curtin, Daxiang Cui, Furong Tian, Natalie Artzi 2015 Institute of Nano Biomedicine and Engineering, Key Laboratory for Thin Film and Microfabrication Technology of the Ministry of Education, Research Institute of Translation Medicine, Shanghai Jiao Tong University, Dongchuan Road 800, 200240 Shanghai, People’s Republic of China

Bioresponsive Antisense Dna Gold Nanobeacons As A Hybrid In Vivo Theranostics Platform For The Inhibition Of Cancer Cells And Metastasis, Chenchen Bao, Joao Conde, James Curtin, Daxiang Cui, Furong Tian, Natalie Artzi

Articles

Gold nanobeacons can be used as a powerful tool for cancer theranostics. Here, we proposed a nanomaterial platform based on gold nanobeacons to detect, target and inhibit the expression of a mutant Kras gene in an in vivo murine gastric cancer model. The conjugation of fluorescently-labeled antisense DNA hairpin oligonucleotides to the surface of gold nanoparticles enables using their localized surface plasmon resonance properties to directly track the delivery to the primary gastric tumor and to lung metastatic sites. The fluorescently labeled nanobeacons reports on the interaction with the target as the fluorescent Cy3 signal is quenched by the gold …


Glad Nanostructured Arrays With Enhanced Carrier Collection And Light Trapping For Photoconductive And Photovoltaic Device Applications, Hilal Cansizoglu 2015 University of Arkansas Little Rock

Glad Nanostructured Arrays With Enhanced Carrier Collection And Light Trapping For Photoconductive And Photovoltaic Device Applications, Hilal Cansizoglu

Theses and Dissertations

Solar energy harvesting has been of great interest for researchers over the past 50 years. Main emphasis has been on developing high quality materials with low defect density and proper band gaps. However, high cost of bulk materials and insufficient light absorption in thin films led to utilization of semiconductor nanostructures in photovoltaics and photonics. Light trapping abilities of nanostructures can provide high optical absorption whereas core/shell nanostructured arrays can allow enhanced charge carrier collection. However, most of the nanofabrication methods that can produce uniform nanostructure geometries are limited in materials, dimensions, and not compatible with industrial production systems. Therefore, …


Rnai-Based Glyconanoparticles Trigger Apoptotic Pathways For In Vitro And In Vivo Enhanced Cancer-Cell Killing, Joao Conde, Furong Tian, Yulan Hernandez, Chenchen Bao, Pedro Baptista, Daxiang Cui, Tobias Stoeger, Jesus M. de la Fuentec 2015 Universidad de Zaragoza, Spain

Rnai-Based Glyconanoparticles Trigger Apoptotic Pathways For In Vitro And In Vivo Enhanced Cancer-Cell Killing, Joao Conde, Furong Tian, Yulan Hernandez, Chenchen Bao, Pedro Baptista, Daxiang Cui, Tobias Stoeger, Jesus M. De La Fuentec

Articles

biotechnology and material science due to their amazing physical, chemical and biological properties. Here, siRNA GlycoNPs (AuNP@PEG@Glucose@siRNA) in comparison to PEGylated GlycoNPs (AuNP@PEG@Glucose) were applied in vitro to a luciferase-CMT/167 adenocarcinoma cancer cell line and in vivo via intratracheal instillation directly into the lung of B6 albino mice grafted with luciferase-CMT/167 adenocarcinoma cells. siRNA GlycoNPs but not PEGylated GlycoNPs induced the expression of pro-apoptotic proteins such as Fas/CD95 and caspases 3 and 9 in CMT/167 adenocarcinoma cells in a dose dependent manner, independent from the inflammatory response, evaluated by bronchoalveolar lavage cell counting. Moreover, in vivo pulmonary delivered siRNA GlycoNPs …


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