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Combination Strategies For Targeted Delivery Of Nanoparticles For Cancer Therapy, Zhonglie He, Kangze Liu, Hugh Byrne, Patrick Cullen, Furong Tian, James Curtin 2019 Technological University Dublin

Combination Strategies For Targeted Delivery Of Nanoparticles For Cancer Therapy, Zhonglie He, Kangze Liu, Hugh Byrne, Patrick Cullen, Furong Tian, James Curtin

Books / book chapters

Pharmaceuticals, and more recently biopharmaceuticals, have become the mainstay for antineoplastic treatments in combination with surgical interventions and radiation therapy. In recent years, advances have been made in the development of nano-technological interventions for the treatment of cancer alone or in combination with existing therapeutic modalities. Nanotechnology used for therapeutic drug delivery and sensitization of photodynamic, sonodynamic and radiotherapy are now being tested in preclinical and clinical trials for the treatment of cancer. This article will review the current state of the art for nanotechnology therapies with an emphasis on targeted drug delivery and the observed and likely benefits when …


Mechanisms And Thermodynamics Of The Influence Of Solution-State Interactions Between Hpmc And Surfactants On Mixed Adsorption Onto Model Nanoparticles, Salin Gupta Patel 2019 University of Kentucky

Mechanisms And Thermodynamics Of The Influence Of Solution-State Interactions Between Hpmc And Surfactants On Mixed Adsorption Onto Model Nanoparticles, Salin Gupta Patel

Theses and Dissertations--Pharmacy

Nanoparticulate drug delivery systems (NDDS) such as nanocrystals, nanosuspensions, solid-lipid nanoparticles often formulated for the bioavailability enhancement of poorly soluble drug candidates are stabilized by a mixture of excipients including surfactants and polymers. Most literature studies have focused on the interaction of excipients with the NDDS surfaces while ignoring the interaction of excipients in solution and the extent to which the solution-state interactions influence the affinity and capacity of adsorption. Mechanisms by which excipients stabilize NDDS and how this information can be utilized by formulators a priori to make a rational selection of excipients is not known.

The goals of …


Fabrication Of Polyelectrolyte Nanoparticles Through Hydrophobic Interaction, Ruginn Porce Catarata 2019 University of Central Florida

Fabrication Of Polyelectrolyte Nanoparticles Through Hydrophobic Interaction, Ruginn Porce Catarata

Electronic Theses and Dissertations

Anticancer drugs like gemcitabine (GEM) are used to treat cancers such as, pancreatic ductal adenocarcinoma (PDAC). However, the use of free gemcitabine yields challenges including cytotoxicity to healthy cells and poor circulation time. By encapsulating GEM in nanoparticles these challenges can be overcome. In this study poly(acrylic acid) (PAA)-GEM nanoparticles are fabricated by coupling GEM onto PAA. The particle formation is driven by the hydrophobic interaction of GEM, which collects in the core of the nanoparticle, forming a PAA shell. The nanoparticles were optimized by studying the PAA/GEM ratio and pH during fabrication. Characteristics of the nanoparticles including size, morphology …


Development Of 3d Printed And 3d Metal-Based Micro/Nanofabricated, And Nano-Functionalized, Microelectrode Array (Mea) Biosensors For Flexible, Conformable, And In Vitro Applications, Charles Didier 2019 University of Central Florida

Development Of 3d Printed And 3d Metal-Based Micro/Nanofabricated, And Nano-Functionalized, Microelectrode Array (Mea) Biosensors For Flexible, Conformable, And In Vitro Applications, Charles Didier

Electronic Theses and Dissertations

Emerging fields such as "Organs on a Chip", disease modeling in vitro, stem cell manufacturing and wearable bioelectronics are demanding rapid development of 3D Microelectrode Arrays (MEAs) for electrical interfacing with biological constructs. The work reported in this thesis focuses on two developmental tracks: "Dynamic 3D MEAs" and metal microfabrication for 3D MEAs. In the first part of the thesis, we explore the capabilities and limitations of 3D printed microserpentines (µserpentines) and utilize these structures to develop dynamic 3D microelectrodes. Analytical modeling of µserpentines flexibility followed by integration into a flexible Kapton® package and PDMS insulation are demonstrated. These 3D …


Nutritional Transporter Mediated Drug Delivery For Cancer, Siddharth S. Kesharwani 2019 South Dakota State University

Nutritional Transporter Mediated Drug Delivery For Cancer, Siddharth S. Kesharwani

Electronic Theses and Dissertations

Recent advancements in nanotechnology have unfolded novel opportunities in medicine, especially in targeted therapeutics and imaging for cancer. However, the majority of the existing nanotechnologies for cancer suffer from shortcomings such as (i) rapid elimination from the systemic circulation before reaching the cancer tissue. (ii) poor tumor accumulation, targeting, and penetration due to inadequate vasculature and extensive extracellular matrix in the tumor. Thus, overcoming these two limitations of nanotechnology is of considerable interests for cancer researchers. In this dissertation, we demonstrate the feasibility of glucose-modified nanoparticles (GLU-NPs) as an efficient cancer targeted-delivery system for enhancing the systemic circulation time and …


Therapeutic Delivery Technology And Its Economic Impact, Paul E. Savas Jr. 2019 Liberty University

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 …


Evaluating The Effects Of Antibody-Conjugated Multi-Walled Carbon Nanotubes In Combination With Microwave Irradiation, Amy Chall 2019 Georgia Southern University

Evaluating The Effects Of Antibody-Conjugated Multi-Walled Carbon Nanotubes In Combination With Microwave Irradiation, Amy Chall

Electronic Theses and Dissertations

Cancer remains one of the largest public health concerns of our day, particularly in developed countries where technological advances have allowed populations to live well into their eighth decade. In America, those in their 80’s have a 1 in 2 chance of developing cancer in their lifetime. Prostate cancer, specifically is the second leading cause of cancer deaths in males. Traditional cancer therapies cause high levels of toxicity to the patient due to mechanisms of action that often attack cancer cells and healthy cells alike. The holy grail of cancer research is to find a treatment that targets the cancer …


Delivery Of Microrna With Cxcr4-Targeted Nanoparticles In Metastatic Cancer Treatment, Ying Xie 2018 University of Nebraska Medical Center

Delivery Of Microrna With Cxcr4-Targeted Nanoparticles In Metastatic Cancer Treatment, Ying Xie

Theses & Dissertations

Metastasis is the main contributor to cancer-associated deaths. Inhibition of CXCR4 emerged as one promising approach in metastatic cancer therapy. MiRNAs represent a new class of therapeutics for cancer treatment through RNA interference-mediated gene silencing. Polymeric CXCR4 antagonist (PCX) is a dual-functional polycation to inhibit CXCR4 and deliver nucleic acids. This dissertation hypothesized that blockade of CXCR4 by PCX combined with delivery of miRNA cooperatively enhances metastatic cancer therapy.

In chapter 1, an overview of CXCR4 inhibition, miRNA delivery and CXCR4 targeted nanomedicine in cancer therapy is given.

Chapter 2 reports that PCX can effectively deliver miR-200c mimic and that …


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 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. …


Strategies Involving The Food-Derived Agent Curcumin To Eliminate Brain Cancer, Sumit Mukherjee 2018 The Graduate Center, City University of New York

Strategies Involving The Food-Derived Agent Curcumin To Eliminate Brain Cancer, Sumit Mukherjee

Dissertations, Theses, and Capstone Projects

Glioblastoma (GBM) is one of the most deadly forms of cancer with a mean 5-year survival rate of ≤5%. We have used the non-invasive strategy of long-term intranasal (IN) delivery of a glioblastoma-directed adduct of curcumin (CC), CC-CD68Ab, into the brain of murine GBM cell line GL261-implanted mice to study the therapeutic effect of CC on GBM remission. The treatment caused GBM tumor remission in 50% of GL261-implanted GBM mice. A similar rescue rate (60%) was also achieved through long-term intraperitoneal (i.p) infusion of a highly bioavailable phosphotidylcholine (PC)-encapsulated formulation of CC, Curcumin Phytosome Meriva (CCP), into the GL261-implanted GBM …


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 injectable …


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 …


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., …


Distribution And Localization Of Novel Iodine Nanoparticles In The Human Glioma 1242 Growing In The Brains Of Mice, Benjamin Billings 2018 University of Connecticut

Distribution And Localization Of Novel Iodine Nanoparticles In The Human Glioma 1242 Growing In The Brains Of Mice, Benjamin Billings

Honors Scholar Theses

Observing and designing the in vivo distribution and localization of therapeutic nanoparticles is an essential aspect of developing and understanding novel nanoparticle- based medical treatments. This study investigates novel PEGylated Iodine-based nanoparticles (INPs), an alternate composition to the more widely researched gold nanoparticles (AuNPs), which may help avoid adverse effects associated with AuNPs, such as potential toxicity and skin discoloration, when used in similar applications. Determining the localization of the novel INPs within murine brains containing human glioma U-1242MG cells is critical in assisting the development of radiation dose enhancement therapy for this aggressive cancer. Radiation dose enhancement utilizes the …


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

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

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 …


Muc4 Based Immunotherapy For Pancreatic Cancer, Kasturi Banerjee 2018 University of Nebraska Medical Center

Muc4 Based Immunotherapy For Pancreatic Cancer, Kasturi Banerjee

Theses & Dissertations

Pancreatic Cancer (PC) is a lethal disease claiming approximately 45000 lives in the US in 2018, and it establishes an elaborate immunosuppressive tumor microenvironment that aids in disease pathogenesis. Immunotherapy has emerged as a strategy to target tumor cells by reprogramming patient’s immune system. Challenges present in PC immunotherapy are: i) identifying a tumor-associated antigen that could be targeted, ii) identifying adjuvants that could efficiently deliver antigens, iii) eliciting robust anti-tumor responses and iv) overcoming peripheral tolerance and immunosuppression elicited by the tumor.

Firstly, we detected circulating autoantibodies to MUC4 present in PC patients and observed that IgM autoantibodies to …


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 Technological University Dublin

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 nm …


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