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
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 ...
Ectopic High Endothelial Venules In Pancreatic Ductal Adenocarcinoma: A Unique Site For Targeted Delivery, 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, 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 ...
Modified Cantilever Arrays Improve Sensitivity And Reproducibility Of Nanomechanical Sensing In Living Cells, 2018 University College London
Modified Cantilever Arrays Improve Sensitivity And Reproducibility Of Nanomechanical Sensing In Living Cells, Samadhan B. Patil, Rajai M. Al-Jehani, Hashem Etayash, Valerian Turbe, Keren Jiang, Joe Bailey, Walid Al-Akkad, Rania Soudy, Kamaljit Kaur, Rachel A. Mckendry, Thomas Thundat, Joseph W. Ndieyira
Pharmacy Faculty Articles and Research
Mechanical signaling involved in molecular interactions lies at the heart of materials science and biological systems, but the mechanisms involved are poorly understood. Here we use nanomechanical sensors and intact human cells to provide unique insights into the signaling pathways of connectivity networks, which deliver the ability to probe cells to produce biologically relevant, quantifiable and reproducible signals. We quantify the mechanical signals from malignant cancer cells, with 10 cells per ml in 1000-fold excess of non-neoplastic human epithelial cells. Moreover, we demonstrate that a direct link between cells and molecules creates a continuous connectivity which acts like a percolating ...
Nanoparticle Microarray For High-Throughput Microbiome Metabolomics Using Matrix-Assisted Laser Desorption Ionization Mass Spectrometry, Rebecca L. Hansen, Maria Emilia Duenas, Torey Looft, Young Jin Lee
A high-throughput matrix-assisted laser desorption/ionization mass spectrometry (MALDI)-MS-based metabolomics platform was developed using a pre-fabricated microarray of nanoparticles and organic matrices. Selected organic matrices, inorganic nanoparticle (NP) suspensions, and sputter coated metal NPs, as well as various additives, were tested for metabolomics analysis of the turkey gut microbiome. Four NPs and one organic matrix were selected as the optimal matrix set: α-cyano-4-hydroycinnamic acid, Fe3O4 and Au NPs in positive ion mode with 10 mM sodium acetate, and Cu and Ag NPs in negative ion mode with no additive. Using this set of five matrices, over two thousand unique ...
Optical Temperature Sensing With Infrared Excited Upconversion Nanoparticles, 2018 North Carolina State University
Optical Temperature Sensing With Infrared Excited Upconversion Nanoparticles, Kory Green, Kai Huang, Hai Pan, Gang Han, Shuang Fang Lim
Open Access Articles
Upconversion Nanoparticles (UCNPs) enable direct measurement of the local temperature with high temporal and thermal resolution and sensitivity. Current studies focusing on small animals and cellular systems, based on continuous wave (CW) infrared excitation sources, typically lead to localized thermal heating. However, the effects of upconversion bioimaging at the molecular scale, where higher infrared intensities under a tightly focused excitation beam, coupled with pulsed excitation to provide higher peak powers, is not well understood. We report on the feasibility of 800 and 980 nm excited UCNPs in thermal sensing under pulsed excitation. The UCNPs report temperature ratiometrically with sensitivities in ...
A Cancer-Targeted Gold Nanoparticle-Based Mri Contrast Agent., 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., 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, 2018 Royal College of Surgeons in Ireland
The Development Of Hydrogels And Nanoparticles For Drug And Cell Delivery To The Distal Airways, Christina Payne
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
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 ...
Cerium Oxide Nanoparticles Inhibit Lipopolysaccharide Inducedmap Kinase/Nf-Kb Mediated Severe Sepsis, 2018 Marshall University
Cerium Oxide Nanoparticles Inhibit Lipopolysaccharide Inducedmap Kinase/Nf-Kb Mediated Severe Sepsis, Mani Maheshwari, Nandini Manne Phd, Shinichi Asano, Eric Blough, Kevin M. Rice, Niraj Nepa,, Erin Fankhanel
The life threatening disease of sepsis is associated with high mortality. Septic patient survivability with currently available treatments has failed to improve. The purpose of this study was to evaluate whether lipopolysaccharide (LPS) induced sepsis mortality and associated hepatic dysfunction can be prevented by cerium oxide nanoparticles (CeO2NPs) treatment in male Sprague Dawley rats. Here we provide the information about the methods processing of raw data related to our study published in Biomaterials (Selvaraj et al., Biomaterials, 2015, In press) and Data in Brief (Selvaraj et al., Data in Brief, 2015, In Press). The data present here provides confirmation of ...
Investigating The Role Of Gold Nanoparticle Shape And Size In Their Toxicities To Fungi, 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
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, 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, 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 ...
Magneto-Electric Nano-Particles For Non-Invasive Brain Stimulation, 2018 Center for Nanomedicine, College of Engineering and Computing, Florida International University, Miami, Florida
Magneto-Electric Nano-Particles For Non-Invasive Brain Stimulation, Kun Yue, Rakesh Guduru, Jeongmin Hong, Ping Liang, Madhavan Nair, Sakhrat Khizroev
This paper for the first time discusses a computational study of using magneto-electric (ME) nanoparticles to artificially stimulate the neural activity deep in the brain. The new technology provides a unique way to couple electric signals in the neural network to the magnetic dipoles in the nanoparticles with the purpose to enable a non-invasive approach. Simulations of the effect of ME nanoparticles for non-invasively stimulating the brain of a patient with Parkinson’s Disease to bring the pulsed sequences of the electric field to the levels comparable to those of healthy people show that the optimized values for the concentration ...
Physiologically Based Pharmacokinetic Modeling Of Nanoceria Systemic Distribution In Rats Suggests Dose- And Route-Dependent Biokinetics, 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, 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
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, 2018 University of Texas MD Anderson Cancer Center
Hyperpolarization Of Silicon Nanoparticles With Tempo Radicals, Jingzhe Hu, Nicholas Whiting, Pratip Bhattacharya
Preparation And Physical Properties Of Functional Barium Carbonate Nanostructures By A Facile Composite-Hydroxide-Mediated Route, 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
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.
Dual Radiosensitization And Anti-Stat3 Anti-Proliferative Strategy Based On Delivery Of Gold Nanoparticle - Oligonucleotide Nanoconstructs To Head And Neck Cancer Cells, 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 ...