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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 …


Towards Elucidation Of The Mechanism Of Biological Nanomotors, Zhengyi Zhao 2016 University of Kentucky

Towards Elucidation Of The Mechanism Of Biological Nanomotors, Zhengyi Zhao

Theses and Dissertations--Pharmacy

Biological functions such as cell mitosis, bacterial binary fission, DNA replication or repair, homologous recombination, Holliday junction resolution, viral genome packaging, and cell entry all involve biomotor-driven DNA translocation. In the past, the ubiquitous biological nanomotors were classified into two categories: linear and rotation motors. In 2013, we discovered a third type of biomotor, revolving motor without rotation. The revolving motion is further found to be widespread among many biological systems. In addition, the detailed sequential action mechanism of the ATPase ring in the phi29 dsDNA packaging motor has been elucidated: ATP binding induces a conformational entropy alternation of ATPase …


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 …


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 …


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 …


Multi-Scale Nanoindentation For Characterization Of Oil Shales, Zachary N. Miller 2016 University of Mississippi

Multi-Scale Nanoindentation For Characterization Of Oil Shales, Zachary N. Miller

Electronic Theses and Dissertations

Studies of the effects of polishing techniques, scale of nanoindentation, and petrophysical properties were conducted on both Woodford and Tuscaloosa Marine Shale. Polishing procedures include both an in-house developed, mechanical sample preparation protocol as well as ion beam milling. The elastic modulus and hardness of each mechanically polished sample was found to have larger value than those that were ion-milled. Additionally, at low loads, the samples resulted in having high standard deviation. This high deviation was found to be significantly reduced by testing at higher loads. The variations in results between mechanically polished and ion beam milled samples is believed …


Radioprotective Cerium Oxide Nanoparticles: Molecular Imaging Investigations Of Conps’ Pharmacokinetics, Efficacy, And Mechanisms Of Action, Philip R. McDonagh III 2016 Virginia Commonwealth University

Radioprotective Cerium Oxide Nanoparticles: Molecular Imaging Investigations Of Conps’ Pharmacokinetics, Efficacy, And Mechanisms Of Action, Philip R. Mcdonagh Iii

Theses and Dissertations

Cerium oxide nanoparticles (CONPs) are being investigated for several anti-oxidant applications in medicine. One of their most promising applications is as a radioprotective drug, an area of research in need due to the severe side effects from radiation therapy. In this work, the potential of CONPs as a radioprotective drug is examined using four criteria: favorable biodistribution/pharmacokinetics, low toxicity, ability to protect normal tissue from radiation damage, and lack of protection of tumor. The mechanisms of action of CONPs are also studied. Biodistribution was determined in radiolabeled CONPs with surface coatings including citrate, dextran T10-amine (DT10-NH2), dextran T10-polyethylene …


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 …


Complex Coacervate-Based Materials For Biomedicine, Sarah L. Perry, Whitney C. Blocher 2016 University of Massachusetts Amherst

Complex Coacervate-Based Materials For Biomedicine, Sarah L. Perry, Whitney C. Blocher

Chemical Engineering Faculty Publication Series

There has been increasing interest in complex coacervates for deriving and trans- porting biomaterials. Complex coacervates are a dense, polyelectrolyte-rich liq- uid that results from the electrostatic complexation of oppositely charged macroions. Coacervates have long been used as a strategy for encapsulation, par- ticularly in food and personal care products. More recent efforts have focused on the utility of this class of materials for the encapsulation of small molecules, pro- teins, RNA, DNA, and other biomaterials for applications ranging from sensing to biomedicine. Furthermore, coacervate-related materials have found utility in other areas of biomedicine, including cartilage mimics, tissue culture scaffolds, …


Interrogating Metabolism In Brain Cancer, Travis Salzillo, Jingzhe Hu, Linda Nguyen, Nicholas Whiting, Jaehyuk Lee, Joseph Weygand, Prasanta Dutta, Shivanand Pudakalakatti, Niki Zacharias Millward, Seth Gammon, Frederick F. Lang, Amy B. Heimberger, Pratip Bhattacharya 2015 The University of Texas MD Anderson Cancer Center

Interrogating Metabolism In Brain Cancer, Travis Salzillo, Jingzhe Hu, Linda Nguyen, Nicholas Whiting, Jaehyuk Lee, Joseph Weygand, Prasanta Dutta, Shivanand Pudakalakatti, Niki Zacharias Millward, Seth Gammon, Frederick F. Lang, Amy B. Heimberger, Pratip Bhattacharya

Nicholas Whiting

Many existing and emerging techniques of interrogating metabolism in brain cancer are at an early stage of development. A few clinical trials that employ these techniques are in progress in patients with brain cancer to establish the clinical efficacy of these techniques. It is likely that in vivo metabolomics and metabolic imaging is the next frontier in brain cancer diagnosis and assessing therapeutic efficacy.


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 …


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 …


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 …


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 …


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. …


Label-Free Surface-Enhanced Raman Spectroscopy-Linked Immunosensor Assay (Slisa) For Environmental Surveillance, vinay bhardwaj 2015 Florida International University

Label-Free Surface-Enhanced Raman Spectroscopy-Linked Immunosensor Assay (Slisa) For Environmental Surveillance, Vinay Bhardwaj

FIU Electronic Theses and Dissertations

The contamination of the environment, accidental or intentional, in particular with chemical toxins such as industrial chemicals and chemical warfare agents has increased public fear. There is a critical requirement for the continuous detection of toxins present at very low levels in the environment. Indeed, some ultra-sensitive analytical techniques already exist, for example chromatography and mass spectroscopy, which are approved by the US Environmental Protection Agency for the detection of toxins. However, these techniques are limited to the detection of known toxins. Cellular expression of genomic and proteomic biomarkers in response to toxins allows monitoring of known as well as …


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., …


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. …


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 …


Enzyme Catalyzed Alginate Nanogels For Drug Delivery, Danna Nichole Sharp 2015 University of Tennessee - Knoxville

Enzyme Catalyzed Alginate Nanogels For Drug Delivery, Danna Nichole Sharp

Masters Theses

Developing nanoscale carriers for the delivery of therapeutics is an important topic of investigation in current biomedical research. As opposed to traditional drug delivery systems, nanoscale systems offer enhanced tissue and cell permeation in addition to reducing drug elimination from the body. Biological based therapeutics such as DNA and proteins are now widely employed in medical applications and research has focused on using nanoscale drug delivery systems to administer these more effectively. Current synthesis methods of nanoscale biotherapeutic carriers face significant challenges. Among these are creating carriers with: sizes between 10-200 nm, low polydispersity, and non-cytotoxic materials. In this thesis, …


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