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Pentablock Copolymer Micelle Nanoadjuvants Enhance Cytosolic Delivery Of Antigen And Improve Vaccine Efficacy While Inducing Low Inflammation, Sujata Senapati, Ross J. Darling, Darren Loh, Ian C. Schneider, Michael J. Wannemeuhler, Balaji Narasimhan, Surya K. Mallapragada 2019 Iowa State University

Pentablock Copolymer Micelle Nanoadjuvants Enhance Cytosolic Delivery Of Antigen And Improve Vaccine Efficacy While Inducing Low Inflammation, Sujata Senapati, Ross J. Darling, Darren Loh, Ian C. Schneider, Michael J. Wannemeuhler, Balaji Narasimhan, Surya K. Mallapragada

Chemistry Publications

As the focus has shifted from traditional killed or live, attenuated vaccines towards subunit vaccines, improvements in vaccine safety have been confronted with low immunogenicity of protein antigens. This issue has been addressed by synthesizing and designing a wide variety of antigen carriers and adjuvants, such as Toll-like receptor agonists (e.g., MPLA, CpG). Studies have focused on optimizing adjuvants for improved cellular trafficking, cytosolic availability, and improved antigen presentation. In this work, we describe the design of novel amphiphilic pentablock copolymer (PBC) adjuvants that exhibit high biocompatibility and reversible pH- and temperature-sensitive micelle formation. We demonstrate improved humoral immunity ...


Combination Therapy: Parp Inhibitor Synergizes The Therapeutic Efficacy Of Doxorubicin In The Treatment Of Prostate Cancer, Momin Ansare 2018 Pittsburg State University

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

Electronic Thesis Collection

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 ...


Ectopic High Endothelial Venules In Pancreatic Ductal Adenocarcinoma: A Unique Site For Targeted Delivery, Baharak Bahmani, Mayuko Uehara, Farideh Ordikhani, Xiaofei Li, Liwei Jiang, Naima Banouni, Takaharu Ichimura, Vivek Kasinath, Siawosh K. Eskandari, Nasim Annabi, Jonathan S. Bromberg, Leonard D. Shultz, Dale L. Greiner, Reza Abdi 2018 Harvard Medical School

Ectopic High Endothelial Venules In Pancreatic Ductal Adenocarcinoma: A Unique Site For Targeted Delivery, Baharak Bahmani, Mayuko Uehara, Farideh Ordikhani, Xiaofei Li, Liwei Jiang, Naima Banouni, Takaharu Ichimura, Vivek Kasinath, Siawosh K. Eskandari, Nasim Annabi, Jonathan S. Bromberg, Leonard D. Shultz, Dale L. Greiner, Reza Abdi

Open Access Articles

BACKGROUND: Nanomedicine offers an excellent opportunity to tackle treatment-refractory malignancies by enhancing the delivery of therapeutics to the tumor site. High endothelial venules (HEVs) are found primarily in lymph nodes or formed de novo in peripheral tissues during inflammatory responses. They express peripheral node addressin (PNAd), which is recognized by the monoclonal antibody MECA79.

METHODS: Here, we demonstrated that HEVs form de novo in human pancreatic ductal adenocarcinoma (PDAC). We engineered MECA79 coated nanoparticles (MECA79-NPs) that recognize these ectopic HEVs in PDAC.

FINDINGS: The trafficking of MECA79-NPs following intravenous delivery to human PDAC implanted in a humanized mouse model was ...


Targeted Delivery Of Bioactive Molecules For Vascular Intervention And Tissue Engineering, Hannah A. Strobel, Elisabet I. Qendro, Eben Alsberg, Marsha W. Rolle 2018 Worcester Polytechnic Institute

Targeted Delivery Of Bioactive Molecules For Vascular Intervention And Tissue Engineering, Hannah A. Strobel, Elisabet I. Qendro, Eben Alsberg, Marsha W. Rolle

Open Access Articles

Cardiovascular diseases are the leading cause of death in the United States. Treatment often requires surgical interventions to re-open occluded vessels, bypass severe occlusions, or stabilize aneurysms. Despite the short-term success of such interventions, many ultimately fail due to thrombosis or restenosis (following stent placement), or incomplete healing (such as after aneurysm coil placement). Bioactive molecules capable of modulating host tissue responses and preventing these complications have been identified, but systemic delivery is often harmful or ineffective. This review discusses the use of localized bioactive molecule delivery methods to enhance the long-term success of vascular interventions, such as drug-eluting stents ...


A Cancer-Targeted Gold Nanoparticle-Based Mri Contrast Agent., Nagwa El-Baz 2018 University of Louisville

A Cancer-Targeted Gold Nanoparticle-Based Mri Contrast Agent., Nagwa El-Baz

Electronic Theses and Dissertations

In oncology, imaging plays a major role in terms of early detection and treatment of most types of cancer. Magnetic resonance imaging (MRI) is mostly used for cancer diagnosis due to its excellent contrast resolution. However, MRI for cancer diagnosis is somewhat limited by its sensitivity. In this thesis, we assessed the ability of theranostic platform consisting of gold nanoparticles functionalized with a cancer targeting aptamer; AS1411 and gadolinium chelate (Dotarem thiol derivative; Gd (III)-DO3A) as a MRI contrast agent to target malignant tumors by enhancing the MRI contrast of the detected tumor. The proposed technology is a novel ...


Evaluation Of Drug-Loaded Gold Nanoparticle Cytotoxicity As A Function Of Tumor Tissue Heterogeneity., Hunter Allan Miller 2018 University of Louisville

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 ...


The Development Of Hydrogels And Nanoparticles For Drug And Cell Delivery To The Distal Airways, Christina Payne 2018 Royal College of Surgeons in Ireland

The Development Of Hydrogels And Nanoparticles For Drug And Cell Delivery To The Distal Airways, Christina Payne

PhD theses

Chronic Obstructive Pulmonary Disease (COPD) is a major public health issue, affecting 64 million people globally. COPD is defined as a lung disease characterised by chronic obstruction of lung airflow that interferes with normal breathing and is not fully reversible. This obstruction is due to a combination of airway and parenchymal damage, associated with an enhanced chronic inflammatory response to noxious particles present in tobacco smoke. Despite the significant evolution of medical treatment options for COPD in the last two decades, it is still an incurable disease. Current interventions include pharmacological agents, which primarily aim for symptomatic control, and lung ...


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 2018 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

Mani Maheshwari

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 ...


Investigating The Role Of Gold Nanoparticle Shape And Size In Their Toxicities To Fungi, Kangze Liu, Zhonglei He, Hugh Byrne, James Curtin, Furong Tian 2018 Dublin Institute of Technology

Investigating The Role Of Gold Nanoparticle Shape And Size In Their Toxicities To Fungi, Kangze Liu, Zhonglei He, Hugh Byrne, James Curtin, Furong Tian

Articles

Gold nanoparticles (GNPs) are increasingly being used in a wide range of applications, and such they are being released in greater quantities into the environment. Consequently, the environmental effects of GNPs, especially toxicities to living organisms, have drawn great attention. However, their toxicological characteristics still remain unclear. Fungi, as the decomposers of the ecosystem, interact directly with the environment and critically control the overall health of the biosphere. Thus, their sensitivity to GNP toxicity is particularly important. The aim of this study was to evaluate the role of GNP shape and size in their toxicities to fungi, which could help ...


Nanoparticle-Mediated Therapeutic Agent Delivery For Treating Metastatic Breast Cancer—Challenges And Opportunities, Yunfei Li, Brock Humphries, Chengfeng Yang, Zhishan Wang 2018 University of Kentucky

Nanoparticle-Mediated Therapeutic Agent Delivery For Treating Metastatic Breast Cancer—Challenges And Opportunities, Yunfei Li, Brock Humphries, Chengfeng Yang, Zhishan Wang

Toxicology and Cancer Biology Faculty Publications

Breast cancer (BC) is the second leading cause of cancer-related death in American women and more than 90% of BC-related death is caused by metastatic BC (MBC). This review stresses the limited success of traditional therapies as well as the use of nanomedicine for treating MBC. Understanding the biological barriers of MBC that nanoparticle in vivo trafficking must overcome could provide valuable new insights for translating nanomedicine from the bench side to the bedside. A view about nanomedicine applied in BC therapy has been summarized with their present status, which is gaining attention in the clinically-applied landscape. The progressions of ...


Engineered Exosomes For Delivery Of Therapeutic Sirnas To Neurons, Reka A. Haraszti 2018 University of Massachusetts Medical School

Engineered Exosomes For Delivery Of Therapeutic Sirnas To Neurons, Reka A. Haraszti

GSBS Dissertations and Theses

Extracellular vesicles (EVs), exosomes and microvesicles, transfer endogenous RNAs between neurons over short and long distances. We have explored EVs for siRNA delivery to brain. (1) We optimized siRNA chemical modifications and siRNA conjugation to lipids for EV-mediated delivery. (2) We developed a GMP-compatible, scalable method to manufacture active EVs in bulk. (3) We characterized lipid and protein content of EVs in detail. (4) We established how protein and lipid composition relates to siRNA delivering activity of EVs, and we reverse engineered natural exosomes (small EVs) into artificial exosomes based on these data.

We established that cholesterol-conjugated siRNAs passively associate ...


Physiologically Based Pharmacokinetic Modeling Of Nanoceria Systemic Distribution In Rats Suggests Dose- And Route-Dependent Biokinetics, Ulrika Carlander, Tshepo Paulsen Moto, Anteneh Assefa Desalegn, Robert A. Yokel, Gunnar Johanson 2018 Karolinska Institutet, Sweden

Physiologically Based Pharmacokinetic Modeling Of Nanoceria Systemic Distribution In Rats Suggests Dose- And Route-Dependent Biokinetics, Ulrika Carlander, Tshepo Paulsen Moto, Anteneh Assefa Desalegn, Robert A. Yokel, Gunnar Johanson

Pharmaceutical Sciences Faculty Publications

Background: Cerium dioxide nanoparticles (nanoceria) are increasingly being used in a variety of products as catalysts, coatings, and polishing agents. Furthermore, their antioxidant properties make nanoceria potential candidates for biomedical applications. To predict and avoid toxicity, information about their biokinetics is essential. A useful tool to explore such associations between exposure and internal target dose is physiologically based pharmacokinetic (PBPK) modeling. The aim of this study was to test the appropriateness of our previously published PBPK model developed for intravenous (IV) administration when applied to various sizes of nanoceria and to exposure routes relevant for humans.

Methods: Experimental biokinetic data ...


Toxicological Assessment Of Nanomaterials: The Role Of In Vitro Raman Microspectroscopic Analysis, Esen Efeoglu, Marcus Maher, Alan Casey, Hugh Byrne 2018 Dublin Institute of Technology

Toxicological Assessment Of Nanomaterials: The Role Of In Vitro Raman Microspectroscopic Analysis, Esen Efeoglu, Marcus Maher, Alan Casey, Hugh Byrne

Articles

The acceleration of nanomaterials research has brought about increased demands for rapid analysis of their bioactivity, in a multi-parametric fashion, to minimise the gap between potential applications and knowledge of their toxicological properties. The potential of Raman microspectroscopy for the analysis of biological systems with the aid of multivariate analysis techniques has been demonstrated. In this study, an overview of recent efforts towards establishing a ‘label-free high content nanotoxicological assessment technique’ using Raman microspectroscopy is presented. The current state of the art for cellular toxicity assessment and the potential of Raman microspectroscopy are discussed, and the spectral markers of the ...


Hyperpolarization Of Silicon Nanoparticles With Tempo Radicals, Jingzhe Hu, Nicholas Whiting, Pratip Bhattacharya 2018 University of Texas MD Anderson Cancer Center

Hyperpolarization Of Silicon Nanoparticles With Tempo Radicals, Jingzhe Hu, Nicholas Whiting, Pratip Bhattacharya

Nicholas Whiting

Silicon-based particles can be hyperpolarized via dynamic nuclear polarization to enhance 29Si magnetic resonance signals. Application of this technique to nanoscale silicon particles has been limited because of the low signal enhancements achieved; it is hypothesized that this is due to the low number of endogenous electronic defects inherent to the particles. We introduce a method of incorporating exogenous radicals into silicon nanoparticle suspensions in order to improve the hyperpolarization of 29Si nuclear spins to levels sufficient for in vivo MR imaging. Calibration of radical concentrations and polarization times are reported for a variety of silicon particle sizes (30−200 ...


Preparation And Physical Properties Of Functional Barium Carbonate Nanostructures By A Facile Composite-Hydroxide-Mediated Route, Tauseef Shahid, Muhammad Arfan, Aurang Zeb, Tayyaba BiBi, Taj Muhammad Khan 2018 Department of Applied Physics, Federal Urdu University of Arts, Science and Technology, Islamabad, Pakistan

Preparation And Physical Properties Of Functional Barium Carbonate Nanostructures By A Facile Composite-Hydroxide-Mediated Route, Tauseef Shahid, Muhammad Arfan, Aurang Zeb, Tayyaba Bibi, Taj Muhammad Khan

Articles

In recent years, nanotechnology has given birth to numerous nanomaterials due to their increased use in various sectors of research and development. To produce these nanomaterials, nanotechnology further has opened several rooms for the potential novel methods. Composite-hydroxide-mediated (CHM) method is one of the recent chemical synthesis routes that have gained considerable importance in research due to their effortlessness and versatile nature, covering a broad range of nanomaterials to prepare.


Multimodal Noncontact Diffuse Optical Reflectance Imaging Of Blood Flow And Fluorescence Contrasts, Daniel Irwin 2018 University of Kentucky

Multimodal Noncontact Diffuse Optical Reflectance Imaging Of Blood Flow And Fluorescence Contrasts, Daniel Irwin

Theses and Dissertations--Biomedical Engineering

In this study we design a succession of three increasingly adept diffuse optical devices towards the simultaneous 3D imaging of blood flow and fluorescence contrasts in relatively deep tissues. These metrics together can provide future insights into the relationship between blood flow distributions and fluorescent or fluorescently tagged agents. A noncontact diffuse correlation tomography (ncDCT) device was firstly developed to recover flow by mechanically scanning a lens-based apparatus across the sample. The novel flow reconstruction technique and measuring boundary curvature were advanced in tandem. The establishment of CCD camera detection with a high sampling density and flow recovery by speckle ...


The Microvascular And Systemic Effects Of Titanium Dioxide Nanoparticle Exposure: A Physiological Perspective, Alaeddin Bashir Abukabda 2018 West Virginia University

The Microvascular And Systemic Effects Of Titanium Dioxide Nanoparticle Exposure: A Physiological Perspective, Alaeddin Bashir Abukabda

Graduate Theses, Dissertations, and Problem Reports

Titanium dioxide nanoparticles (nano-TiO2) are one of the most widely used engineered nanomaterials (ENM). Their ubiquitous inclusion warrants a more thorough understanding of their toxicity, particularly in sensitive populations such as pregnant women and the developing fetus.

The aim of the first study was to determine the most sensitive segments of the vasculature to pulmonary ENM exposure. Macrovascular function was investigated in the thoracic aorta, common femoral artery and 3rd order mesenteric arterioles using wire myography. Microvascular function was assessed in 4th and 5th order mesenteric arterioles via pressure myography. Nano-TiO2 exposure induced impairments in ...


Size-Dependent Inhibitory Effects Of Antibiotic Drug Nanocarriers Against Pseudomonas Aeruginosa, Feng Ding, Preeyaporn Songkiatisak, Pavan Kumar Cherukuri, Tao Huang, Xiao-Hong Nancy Xu 2018 Old Dominion University

Size-Dependent Inhibitory Effects Of Antibiotic Drug Nanocarriers Against Pseudomonas Aeruginosa, Feng Ding, Preeyaporn Songkiatisak, Pavan Kumar Cherukuri, Tao Huang, Xiao-Hong Nancy Xu

Chemistry & Biochemistry Faculty Publications

Multidrug membrane transporters (efflux pumps) are responsible for multidrug resistance (MDR) and the low efficacy of therapeutic drugs. Noble metal nanoparticles (NPs) possess a high surface-area-to-volume ratio and size-dependent plasmonic optical properties, enabling them to serve both as imaging probes to study sized-dependent MDR and as potential drug carriers to circumvent MDR and enhance therapeutic efficacy. To this end, in this study, we synthesized three different sizes of silver nanoparticles (Ag NPs), 2.4 ± 0.7, 13.0 ± 3.1, and 92.6 ± 4.4 nm, functionalized their surface with a monolayer of 11-amino-1-undecanethiol (AUT), and covalently conjugated them with ...


Dual Radiosensitization And Anti-Stat3 Anti-Proliferative Strategy Based On Delivery Of Gold Nanoparticle - Oligonucleotide Nanoconstructs To Head And Neck Cancer Cells, Surong Zhang, Suresh Gupta, Thomas J. Fitzgerald, Alexei A. Bogdanov Jr. 2018 University of Massachusetts Medical School

Dual Radiosensitization And Anti-Stat3 Anti-Proliferative Strategy Based On Delivery Of Gold Nanoparticle - Oligonucleotide Nanoconstructs To Head And Neck Cancer Cells, Surong Zhang, Suresh Gupta, Thomas J. Fitzgerald, Alexei A. Bogdanov Jr.

Radiology Publications and Presentations

Constitutively activated signal transducer and activator of transcription 3 (STAT3) factor is an important therapeutic target in head and neck cancer (HNC). Despite early promising results, a reliable systemic delivery system for STAT3- targeted oligonucleotide (ODN) drugs is still needed for future clinical translation of anti-STAT3 therapies. We engineered and tested a novel ODN duplex/gold nanoparticle (AuNP)-based system carrying a therapeutic STAT3 decoy (STAT3d) payload. This strategy is two-pronged because of the additive STAT3 antagonism and radiosensitizing properties of AuNP. The specificity to head and neck cancer cell surface was imparted by using a nucleolin aptamer (NUAP) that ...


Hyperthermia As A Cancer Treatment- From Theory To Practice, Graham Fullerton 2018 Claremont McKenna College

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 ...


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