Conference Schedule

Day1: July 12, 2018

Keynote Forum

Biography

Julia Ljubimova is Professor of Neurosurgery and Biomedical Sciences and Director of Nanomedicine Research Center, Department of Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, USA. She has been working in clinical and basic cancer research during her entire career. Her major scientific discoveries are: 1) The cancer biomarkers as tools for developing new nanomedicine imaging agents and drugs against primary and metastatic tumours and 2) The development of nano imaging and therapeutic agents that are crossing multiple biological barriers including blood brain barrier (BBB). Nano immunology and nano toxicology are novel important subjects of the fight against tumours and inflammation, which are currently studied in the Nanomedicine Research Center. Her research is supported by National Institutes of Health/National Cancer Institute, private and industry grants. She is the author of over 100 publications, reviews and book chapters as well as an inventor on twelve issued patents, and patent applications.

Abstract

Checkpoint inhibitors, anti-CTLA-4 and/or anti-PD-1 antibodies cannot activate brain anti-tumor immune response because of their inability to cross blood brain barrier (BBB). A new generation of nanoconjugates that pass BBB and activate systemic and local brain tumor immune systems was developed.

Synthesis of immuno-nanoconjugates. Immuno-nanoconjugates (INC) crossing BBB, P/PEG/msTfR/anti-CTLA-4 and P/PEG/msTfR/anti-PD-1 were synthesized. They are based on natural polymer, poly β(L-malic acid) (P), and contain anti-transferrin receptor antibody (MsTfR). Physico-chemical, pharmaceutical, and toxicological parameters of INCs were determined.

Brain tumor treatment. Syngeneic GL261 glioma cells (20,000) were intracranially inoculated into C57/BL mice. Six treatment groups were injected with either PBS, anti-PD-1 and anti-CTLA-4 as a control, or polymer-conjugated anti-PD-1(P/PD-1), anti-CTLA-4 (P/CTLA-4) or a combination of polymers with antibodies, (P/CTLA-4 + P/PD-1) at 10 mg/kg, 5 times I.V. Immuno-nanoconjugates P/CTLA-4 and P/PD-1 significantly improved survival of brain tumor-bearing mice compared to free anti-CTLA-4 and anti-PD-1 (p<0.04 and p<0.004, respectively). The combination P/CTLA-4 + P/PD-1 showed the highest survival efficacy compared with CTLA-4, PD-1, and PBS groups (p<0.001, p<0.04, and p<0.0001, respectively).

Flow cytometry analysis of T cell population in the brain tumor revealed reduction of the total number of CD4+ T-cells in animals treated with P/PD-1 and combination P/CTLA-4 + P/PD-1. The fraction of Tregs (CD4+FOXP3+) was also reduced by all polymer conjugates compared to free antibodies. Activation of CD8+ T-cells (CD8+IFNγ+ and CD8+CD69+) was increased by polymer-conjugated anti-CTLA-4/PD-1 and combination therapy. Animals treated with polymer-conjugated anti-PD-1 and combination treatment showed significant decrease in PD-1 expression by CD8+ cells compared to controls.

Multiplex assay to measure cytokine response to treatment demonstrated significant increase in the expression of IL-1β, IL-2, IL-10, TNFα, IL-6, IL-12, and IFNγ in the brain and serum after combination therapy.

Conclusion: Brain tumor treatment with immuno-nanoconjugates that can cross BBB significantly increased animal survival.

Support: NIH grants U01 CA151815, R01 CA136841, CA206220

Biography

Tamara Minko, PhD is a Distinguished Professor and Chair of the Department of Pharmaceutics at Rutgers, The State University of New Jersey and member of the Cancer Institute of New Jersey. Her current research interests include drug and nucleic acids delivery, nanotechnology, personalized nanomedicine, biopharmaceutics, imaging and molecular targeting. She is an Author and Co-author of more than 400 publications. Her Hirsch factor is above 50. She is a President of Controlled Release Society (CRS), an elected Fellow of three organizations: CRS, American Association of Pharmaceutical Scientists (AAPS), and American Institute for Medical and Biomedical Engineering (AIMBE); recipient of numerous awards, Executive Editor of Advanced Drug Delivery Reviews, Editor of Pharmaceutical Research, member of editorial board of more than ten scientific journals. Her research is supported by grants from NIH, NSF, DOD and other national and international sources.

Abstract

Directing anticancer agents specifically to tumours and/or cancer cells by targeting specific extracellular receptors fulfils the following three most important tasks: (1) preventing or at least substantially limiting adverse side effects on healthy tissues (2) enhancing drug internalization by cancer cells and (3) overcoming (at least in part) resistance mechanisms that are based on the active efflux of exogenous drugs from cancer cells. We developed several tumour-targeted nanoscale-based formulations: various nanocarriers (liposomes, lipid nanoparticles, dendrimers, polymers, quantum dots, mesoporous silica and super magnetic iron oxide nanoparticles); different anticancer drugs (doxorubicin, paclitaxel, camptothecin, and cisplatin); suppressors of cellular drug resistance and tumour grows (antisense oligonucleotides or siRNA targeted to BCL2, MDR1, MRP1, HIF1A, CD44 mRNA); and tumour-targeting agent - luteinizing hormone-releasing hormone (LHRH). The proposed nanotherapeutics were tested in vitro and in vivo using established lung and ovarian cancer cell lines and highly metastatic cancer cells isolated from malignant intraperitoneal ascites from patients with advanced ovarian carcinoma. These cells were used to initiate orthotopic models of lung and ovarian cancers in nude mice that were often accompanied by the development of metastases. Tumour-targeted nanoscale-based drug formulations were delivered intravenously and intraperitoneally (for ovarian cancer) or intravenously and by inhalation (for lung cancer). Treatment with the developed therapeutics led to the suppression of targeted proteins, efficient induction of cell death, effective tumour shrinkage, prevention the development of metastases and limitation of adverse side effects.

Biography

After his PhD in physics, Andreas Seifert moved to optical industry and had been working as head of department with Carl Zeiss (Germany) from 1998 to 2007, managing technology for EUV lithography and being responsible for synchrotron and space optics. In 2007 he became group leader in the Department of Microsystems Engineering, University of Freiburg. His research lines covered optical and biomedical microsystems, specifically for cardiovascular monitoring and tissue differentiation. In 2015 he gained the position of an Ikerbasque Professor at CIC nanoGUNE in San Sebastián (Spain) and is leading the Nanoengineering Group. The research concentrates on photonics/plasmonics for biomedical diagnostics with the strategy of bridging the gap between fundamental science and real-life applications and accelerating technology transfer. The most prestigious awards he received are the ‘Rudolf Kingslake Medal and Prize 2013’ and the ‘Carl Zeiss Innovation Award 2006’.

Abstract

Microsystems engineering, nanotechnology and bio nanotechnology open new opportunities in medical diagnostics and treatment. For the first time, physics and engineering can be combined with medicine and biology on a very fundamental level. Modern technology allows approaching physiological processes in situ and gives access to the interior of the body by non-invasive techniques. A variety of optical and photonic methods have been developed on a high scientific level, and also on a well-engineered technical level. Bringing novel methods and technology into the market turns out to be a major challenge, and most of all developments and approaches do not reach the market, even though they show great performance and potential. The key to access the market is developing strategies for the acceleration of technology transfer and to follow those before the idea is realized in the lab. Communication and understanding of the different languages of scientists, engineers, clinicians and industrial partners is crucial for bridging the gap between academia and industry. The market or end user needs are the driving force to set the direction of successful developments from the lab to the market. The talk highlights examples of photonic methods employed in medical diagnostics, as for example the development of a combined Raman-FTIR spectroscopy system to detect Alzheimer’s disease in an early stage; the development of method and instrumentation for in situ and real-time tissue differentiation during tumor resection; a photonic approach for continuous intrapartum fetal monitoring to reduce risks during delivery. In collaboration with clinical and industrial partners, the Nanoengineering Group at nanoGUNE develops photonic and plasmonic methods and systems for medical diagnostics, food control, environmental monitoring, and consumer goods for sports industry.

Tracks

  • Nanobiotechnology | NanoMedicine | Nanopharmaceuticals | Nano-Chemistry | Nanodevices andNanosensors | Advancement in Nanotechnology
Location: Madrid+Lisbonne
Speaker

Andreas Seifert

CIC Nanogune, Spain

Chair

Speaker

Jinrich Kopecek

University of Utah, USA

Co Chair

Biography

Jindrich Kopecek received his PhD in Macromolecular Chemistry from the Institute of Macromolecular Chemistry (IMC) and DSc in Chemistry from the Czechoslovak Academy of Sciences (CAS), Prague, Czech Republic. He has done his Post-doctoral studies at the National Research Council of Canada. He served as Laboratory Head at IMC CAS and is currently, Distinguished Professor of Bioengineering and Distinguished Professor of Pharmaceutical Chemistry at the University of Utah. He serves on Editorial Boards of 14 international scientific journals. He is an elected member of the US National Academy of Engineering. His research interests are focused on biorecognition of macromolecules, bioconjugate chemistry, drug delivery systems, and self-assembled biomaterials.  Hydrogels from his laboratory have been in clinical use and HPMA copolymer - anticancer drug conjugates in clinical trials. His Hirsch index is 87; his publications have been cited 26,900 times.

Abstract

The address will be based on our strong belief that the future of science in general and smart biomaterials and nanomedicines in particular is in the interdisciplinary approach to hypotheses formulation and problem solving. Nanoscience moved from copying/mimicking nature’s design to modify it and designing bioactive materials. Our understanding of the relationship between structure and properties reached levels needed for the design of totally new materials different from those in nature. The latter approach has the highest potential for scientific and application breakthroughs in the near future. The nanomedicine field needs new ideas, so it can continue to enhance basic scientific knowledge and translate the laboratory and animal model work into humans. One new concept is called drug-free macromolecular therapeutics (DFMT). The design of DFMT is based on molecular biorecognition, which is at the center of all biological processes. Several therapeutic systems were designed that do not contain a low molecular weight drug, but their therapeutic efficacy is based on a combination of a macromolecule with a biorecognition domain. Biological activity is a result of one or more biorecognition events. The majority of studied systems are based on the crosslinking of receptors at the cell surface of blood cancer cells. Other systems target E-selectin receptors in the vasculature or focus on the biomineralization around cancer cells mediated by receptor – ligand recognition.

Biography

Chang-Guo Zhan is an Endowed Professor of Pharmaceutical Sciences and Director of Molecular Modeling and Biopharmaceutical Center in the College of Pharmacy, University of Kentucky. He also serves as Director of Chemoinformatics and Drug Design Core of the Center for Pharmaceutical Research and Innovation at the University of Kentucky. His lab has successfully designed and discovered several promising therapeutic candidates, including two in Phase II clinical trials; one has received the Breakthrough Therapy Designation by the FDA. He is a winner of 2005 Emerging Computational Technology Prize, American Chemical Society (ACS) Division of Computers in Chemistry and is the current recipient of the NIDA Translational Avant-Garde Award from the NIH. He was elected AAPS Fellow in 2010 and won 2016 AAPS Research Achievement Award in Drug Discovery and Development Interface. He is also a UK Chapter Inductee of the National Academy of Inventors (NAI).

Abstract

In this talk, I will first briefly discuss the general strategies and integrated computational-experimental approaches used to understand the detailed molecular mechanisms of increasingly complex biological systems (such as those related to cancers, HIV virus, neurodegenerative diseases, inflammation, cardiovascular diseases, and drug addiction) and perform mechanism-based design, discovery, and development of novel drugs including nanoparticles. I will also discuss the general trend of rational drug design and discovery through specific examples of our integrated efforts from understanding molecular mechanism to clinical development. The presentation will show how powerful understanding the detailed molecular mechanism and mechanism-based computational design are in the current drug design, discovery, and development. The integrated computational-experimental approaches are of great value not only for small-molecule drug discovery, but also for discovery and development of novel, therapeutically promising nanoparticles. Integrated computational-experimental drug design and discovery efforts have led to exciting discovery of promising drug candidates, including our designed novel drugs in Phase II clinical trials; one has received the Breakthrough Therapy Designation by the FDA. 

Biography

Juan Sanchez-Ramos received a PhD in Pharmacology and Physiology from the University of Chicago and a Medical Degree (MD) from the University of Illinois.  He trained in Neurology at the University of Chicago and as a Fellow in Movement Disorders at the University of Miami. Currently, he is a Professor of Neurology at the University of South Florida in Tampa where he holds the Helen Ellis Endowed Chair for Parkinson's disease Research and is Director of the HDSA Center of Excellence for Huntington’s disease.  He is also Medical Director of the non-profit Parkinson Research Foundation based in Sarasota FL.  In addition to teaching and attending to patients with Movement Disorders, he has directed basic research projects in neurodegeneration, neurotoxicology, adult stem cell biology and presently is focused on novel approaches for non-invasive delivery of gene therapy to brain.

Abstract

The intranasal route of drug delivery has traditionally been used to administer small, lipophilic drugs that are rapidly absorbed into capillaries of the nasal epithelium, resulting in rapid onset of CNS actions.  Many neuro-therapeutic agents, especially polynucleotides and proteins, do not readily cross the blood-brain barrier and cannot survive intact in the gut or blood.  Hence, gene therapy for brain disorders has required direct neurosurgical microinjection or infusion into brain or cerebrospinal fluid.  However, recent research has demonstrated direct nose-to-brain delivery of relatively large molecules, including neurotrophins (NGF and insulin-like growth factor [IGF]-1), neuropeptides, cytokines (interferon β-1b and erythropoietin as well as polynucleotides (DNA plasmids and genes). The present report describes development of a novel manganese-chelate nanocarrier system for direct nose-to-brain delivery of small interfering RNA (siRNA) or DNA.  The manganese (Mn) chelate Mangafodopir served 2 functions: 1) as a marker of the NPs for intracerebral tracking with magnetic resonance imaging (MRI) and 2) as a cross-linker of the chitosan matrix in the nanocarrier structure. Using high field small animal MRI, the Mn-tagged NPs were visualized on T1-weighted images and were found to penetrate from nasal epitheliaum into olfactory bulb and across brain regions following intranasal instillation of the nanocarriers.  In addition, Mn content of the nanocarrier did not impede the functional activity of siRNA directed against green fluorescent protein eGFP in transgenic green mice.  Expression of eGFP mRNA in transgenic green mice was decreased by at least 50% in four brain regions. Those brain regions also exhibited significantly increased Mn signal in T1-weighted MR images. In separate experiments, we showed that mNPs loaded with dsDNA encoding the red fluorescent protein (RFP) was expressed in corpus striatum and other regions following intranasal administration.  Hence, this novel nanocarrier system permitted in vivo tracking of the therapeutic agent and was effective in delivering nucleic acid payloads that exhibited the expected activity in brain tissue.

Biography

Shengyong Xu received his BSc in Physics from the Peking University in 1988 and PhD from Department of Physics, National University of Singapore in 1999. He is currently a professor with Department of Electronics, School of Electronics Engineering and Computer Sciences, Peking University. He has published more than 200 journal and conference papers. His group currently works on the physics of electrical communication among neuron cells and normal cells, temperature sensing at the cell and sub-cell levels, as well as electrostatic tweezers at micro-nano-scales. 

Abstract

Optical nano-thermometers have been well developed to measure the temperature distribution in live cells. Nano-sized indicators such as proteins, organic dyes, quantum dots, polymer particles and nano-diamond, are injected into live cells, and the change in intensity, peak position or lifetime of luminescence spectra for the nano-indicators are used to reveal the change of local temperatures. However, the results are remarkably affected by local environment, e.g., pH value, cellular viscosity and ion concentration in the cytosol, thus causing controversial arguments. Here, we report direct measurement results for the temperatures of individual cultured cancer cells. By using double-stabilized measurement system and array of micro-scale thin-film thermocouples, we have reduced the system thermal noise down to ±5 mK and observed local increments in temperature for individual live cells in the range of 30-280 mK. With further improvements, e.g., by using arrays nano-scaled thermocouples, the current method is promising for real-time 2D mapping for the local temperatures of a single cell.

Biography

Aharon Gedanken obtained his PhD from Tel Aviv University, Israe and later completed his Postdoctoral Research at USC in Los Angeles. He got a Lecturer position at BIU on Oct. 1975. In 1994, he switched his research interest from Spectroscopy to Nanotechnology. His special synthetic methods of nanomaterials include: Sonochemistry, Microwave Superheating, Sonoelectrochemistry, and Reactions under Autogenic Pressure at Elevated Temperatures (RAPET). Since 2004, he is mostly focused on the applications of nanomaterials. Gedanken has published 785 peer-reviewed manuscripts in international journals. His H-Index is 83. He was a partner in five EC FP7 projects one of them, SONO, was coordinated by him. This project was announced by the EC as a Success Story. He was the Israeli representative to the NMP (Nano, Materials, and Processes) committee of EC in FP7. He was awarded the prize of the Israel Vacuum Society in 2009 and the Israel Chemical Society for excellence in Research in Feb 2013.

Abstract

Sonochemistry is our deposition method for imparting unique properties to the desired substrates. It was applied first to coat a large variety of textiles (cotton, polyester, nylon wool and more) with anti-bacterial Nanoparticles (NPs). Excellent adherence to the textiles was demonstrated in withstanding 65 washing cycles in Hospital washing machines. In the current presentation its power will be demonstrated in the deposition of antimicrobial NPs on medical devices such as catheters, contact lenses, cochlear electrodes, and silicon-implants. It was also deposited on artificial teeth by the sonic irradiation and avoided the formation of biofilm of s. mutans. The NPs that have been used in this research are ZnO, CuO, Cu0.89Zn0.11O and MgF2. For the catheters too, in vivo experiments were conducted. The first experiment conducted in Israel where 5 coated and 5 uncoated silicon catheters were installed in rabbits that were hanged during the 7 days of the experiment. The second was done in Synovo, Tubingen where 15 coated and 15 uncoated catheters were inserted in the rabbits which were free to run around. In both cases the coated catheters have avoided the formation of biofilm on the catheters in comparison with the appearance of urine contamination after day 4. Good results were obtained in all the above mentioned medical devices.

Biography

Abraham J Domb, is a Professor for Medicinal Chemistry and Biopolymers at the Faculty of Medicine of the Hebrew University, Jerusalem. He earned Bachelor’s degrees in Chemistry, Pharmaceutics and Law from Bar-Ilan and Hebrew University and PhD degree in Chemistry from Hebrew University. He did his Postdoctoral training at MIT/Harvard and was R&D Manager at Nova Pharm. Co. Baltimore US from 1988-1992. Since 1992, he is a Faculty member at the Hebrew University with interests on Biopolymer synthesis and applications, Biodegradable polymers, Drug delivery systems, Medicinal Chemistry and Forensic sciences. During 2007-2012, he served as Head of the Division of Identification and Forensic Sciences (DIFS), Israel Police. Since April 2014, he is also President of the Jerusalem College of Engineering.

Abstract

Pharmaceutical formulations are a key for the effectiveness of therapeutic agents. Nanotechnology provides a new direction to improve the solubility, stability and bioavailability of various active agents. Incorporation of bioactive molecules into nano-constructs improves their ability to safely cross biological membranes such as the GI tract, BBB, and skin. Nanoparticles made of lipid components, natural or synthetic polymers, carbon, metals and inorganic materials, have been used as drug carriers. Recently, exosomes have been used as natural carriers to direct drug loads to certain body sites. Nucleotide and protein based biological drugs require suitable nano-delivery systems that protect them from deterioration and direct them into specific cells and organs. In addition to the delivery of drugs, nanoparticles have been used as diagnostic agents and as carriers of combined diagnostic and therapeutic agents. The various nano-delivery systems should be tailored to fit the route of administration. The various nano-constructs that have been used for the delivery of active agents and diagnostics by different routes of administration will be discussed.

Biography

Nouf Nawaf Mahmoud completed his Bsc in Pharmacy (the University of Jordan), MSc in Clinical Pharmacy (the University of Jordan) and a PhD in Pharmaceutical Technology (the University of Jordan) before joining the academic staff at Al-Zaytoonah University of Jordan. He is an Assistant Professor of Pharmaceutics at the faculty of Pharmacy and a member of Quality Assurance committee at the faculty. His research focuses on the Nanotechnology and its biomedical applications, understanding the nano-bio interface and in particular the gold nanoparticles-skin interactions and developing advanced trasdermal delivery nano systems.

Abstract

The antibacterial activity of gold nanorod (GNR) suspensions of different surface functionalities was investigated against standard strains of Staphylococcus aureus and Propionibacterium acnes, taking into consideration two commonly overlooked factors: the colloidal stability of GNR suspensions upon mixing with bacterial growth media and the possible contribution of impurities/molecules in GNR suspensions to the observed antibacterial activity. The results demonstrated that cationic polyallylamine hydrochloride (PAH)-GNR were severely aggregated when exposed to bacterial growth media compared to other GNR suspensions. In addition, the free cetyltrimethylammonium bromide (CTAB) present in GNR suspensions is most likely the origin of the observed antibacterial activity. However, the antibacterial activity of GNR themselves could not be excluded. Probing these two critical control studies prevents misinterpretations and artifacts of the antibacterial activity of nanoparticles. Unfortunately, these practices are usually ignored in the published studies and may explain the significant conflicting results. In addition, this study indicates that GNR could be a promising candidate for the treatment of skin follicular diseases such as acne vulgaris.

Biography

Sudhir Kumar Sharma obtained his Masters’ degree (MSc Physics and M. Tech-Materials) from Department of Physics, Barkatullah University Bhopal, India. He received his PhD from the Indian Institute of Science Bangalore, India. He joined as Postdoc fellow at Centre for Nano Science and Engineering (CeNSE), IISc. Bangalore, India. Later he moved to New York University Abu Dhabi UAE (NYU Abu Dhabi) as a Research Associate in 2013. Currently, he is working as a Research Scientist at NYU Abu Dhabi. His publication record includes more than 30 journals and 60 conference presentations. His research interest includes implementation of supercritical technologies for nanoparticle synthesis, smart materials for micro-sensors and actuators, micro/nano- fabrications, vacuum science, and thin film technology.

Abstract

One of the major unsolved problems in pharmaceutical drug development is the poor water solubility of many active pharmaceutical ingredients (APIs) and hence reduced bioavailability. One of the preferred strategies to address this problem was to leverage the increased solubility with decreasing drug particle size. However, an ideal solution would be to eliminate the problem of solubility entirely, by reducing the API size to clusters of a few molecules, bound by weak, Vander Waal’s forces that would readily dissociate into molecules, during enteral or parenteral drug delivery process. In order to have commercial impact, such molecular clusters should also be produced in sufficiently high yield.  In our research, we have successfully addressed both these challenges. We report the precipitation of molecular clusters of ibuprofen using a rapid expansion of super critical solution (RESS) system. Our custom designed liquid N2 cooled collection process of the molecular clusters embedded in dry ice, resulted in yields of up to 80% (w/w). Ambient dissolution of the dry ice in deionized water resulted in a stable dispersion, for up to six months, as confirmed by DLS and AFM characterizations. DLS measurements showed that PEI surfactant (Mw ~400,000) produced the smallest particle size of 7 nm, with a narrow size distribution of ±3 nm. Drop casting of these dispersions on silicon and sapphire substrates resulted in high quality, liquid like viscous films as observed by optical microscopy and AFM. XRD and confocal Raman characterizations confirmed that the molecular clusters retained their chemical identity of ibuprofen. Besides its scientific importance, this invention is expected to open up new drug delivery platforms.

Day2: July 13, 2018

Keynote Forum

Biography

Chantal Pichon is Full Professor at the University of Orleans (France). She has completed PhD in Cellular Biology and Microbiology (1991) at the University of Aix-Marseille before spending 2 years at the AFRC, Cambridge-UK as Post-doc fellow. She is performing her research activities at the Center for Molecular Biophysics of CNRS where she is coordinating the department of Cell Biology and Innovative therapies. Her lab is the pioneer of histidine-based nanoparticles and has developed novel strategies to improve uptake by chemical targeting and/or ultrasound trigger of nucleic acids. These last years, they are focusing their research on RNA as therapeutics. Chantal Pichon has a track-record of 108 publications and has obtained 20 grants (European, national, industrial and charities grants).

 

Abstract

In these last years, we are witnessing the emergence of new class of biopharmaceuticals based on messenger RNA (mRNA). One of the most promising applications of mRNA is their use as vaccines. Any antigenic protein can be encoded by mRNA allowing the development of preventive and therapeutic vaccines to fight against infections, cancer and allergies. Messenger RNA offers a strong safety compared to DNA because it cannot be integrated in host genome. The translation machinery being in the cytosol, mRNA expression does not require nuclear import which is of benefit for hard to transfect cells as dendritic cells. By contrast to peptides, they lack major histocompatibility haplotype restriction. Moreover, mRNA can be recognized by pattern recognition receptors conferring them immunostimulatory properties. But, their recognition by RNA sensors has a negative impact on their translation. The high sensitivity of mRNA for degradation slowed down its in-situ applications in their early use. Therefore, different strategies have been proposed to produce mRNA tailored to be self adjuvanting, to improve the stability and translation and to enhance the immune response. Many reports including ours have demonstrated that mRNA vaccines have proved preclinical efficacy. I will review the current knowledge regarding crucial aspects that should be considered when developing mRNA-based vaccines. Promises and challenges for clinical trials will be also discussed.

Biography

Stephen D Miller is the Judy E Gugenheim Research Professor of Microbiology-Immunology at Northwestern University Feinberg School of Medicine in Chicago.  He received his PhD in 1975 from the Pennsylvania State University and did Postdoctoral training at the University of Colorado Health Sciences Center before joining the faculty at Northwestern in 1981 where he currently serves as Director of the Northwestern University Interdepartmental Immunobiology Center.  He is internationally recognized for his research on pathogenesis and regulation of autoimmune diseases.  He has published over 390 journal articles, reviews and book chapters and has trained multiple generations of scientists. His work has significantly enhanced understanding of immune inflammatory processes underlying chronic autoimmune disease employing animal models of multiple sclerosis (MS) and Type 1 diabetes (T1D).  His work has focused on the study of the cellular and molecular mechanisms underlying treatment of established T cell-mediated autoimmune diseases using antigen-specific immune tolerance.  His current work is geared to translate the use of antigen-linked biodegradable PLG nanoparticles for the treatment of human immune-mediated diseases including autoimmunity, allergy and tissue/organ transplantation.

Abstract

Type 1 diabetes (T1D) is mediated by destruction of pancreatic b cells by CD4 and CD8 T cells specific for epitopes on numerous diabetogenic autoantigens resulting in loss of glucose homeostasis. The ideal solution for treatment of T1D is the restoration of immune tolerance prior to significant β cell loss. We therefore explored the efficacy and mechanisms of restoration of immune tolerance using the intravenous infusion of diabetogenic epitopes attached to or encapsulated within 500nm biodegradable carboxylated poly (lactide-co-glycolide) (PLG) nanoparticles. Employing adoptive transfer models of T1D induced by the transfer of activated diabetogenic CD4+ BDC2.5 chromagranin A-specific and CD8+ NY8.3 IGRP-specific TCR transgenic T cells; we demonstrate the ability of PLG nanoparticles (either surface coupled with or encapsulating the cognate diabetogenic peptides) to rapidly and efficiently restore tolerance in NOD SCID recipients of both activated CD4 and/or CD8 T cells in an antigen-specific manner. Further, Ag-PLG-induced peripheral tolerance initiation and maintenance were demonstrated to operate via several overlapping, but independent pathways including regulation via negative-co-stimulatory molecules (namely CTLA-4 and PD-1) and the systemic induction of peptide-specific Tregs which were shown to be critical for long-term maintenance of tolerance in recipients of BDC2.5 CD4 diabetogenic T cells. The net result of the tolerance therapy was inhibition of both trafficking of effector diabetogenic cells to, and their release of proinflammatory cytokines within the pancreas, concomitant with selective retention of effector cells in the spleens of recipient mice. These results clearly demonstrate the unique ability of Ag-PLG-induced tolerance to halt/reverse b cell destruction in mice with high numbers of activated effector diabetogenic CD4 and CD8 T cells.

Biography

Aaron Claeys is a young Entrepreneur and Owner of Nanex Company. He is a CEO and Nanotech Researcher running his own R&D unit with expertise in multifunctional Nano coatings to make materials smart, durable and more sustainable. He is also specialising in water and air purification true nanotechnology to face current challenges worldwide.

Abstract

My talk will not be about my technical knowledge in my field of research; it will be about my experience and insights as a researcher and entrepreneur about the nanotech industry. As of my opinion sharing most important insights when running a nanotech business / R&D unit, my presentation includes short introduction, safety measurements when working with Nano particles and suppliers, working true the value chain, what’s your net value or impact? Your personal and company mission, how to overcome difficult times when innovating, things to be considered to form your long-term strategy and community-based value creation, connecting minds to face current challenges.

Tracks

  • NanoMaterials | NanoRobotics | NanoElectronics | Cellular and subcellular Nanotechnology | Major Challenges in Nanobiotechnology
Location: Madrid+Lisbonne
Speaker

Chantal Pichon

University of Orleans, France

Chair

Speaker

Stephen D. Miller

Northwestern University, USA

Co Chair

Biography

Twana Mohammed M Ways has completed his MSc from University of Sulaimani. He is a PhD student at University of Reading, UK. He has published 1 review paper.

Abstract

Mucosal drug delivery is a technique for administration of drugs through mucous membranes lining the gastrointestinal tract, respiratory tract, urogenital tract and ocular surface. It has several advantages including increased residence time at the site of absorption/action, decreased administration frequency and thus better patient compliance. However, with conventional mucosal drug delivery these could only be achieved to a certain degree. Thus, in this study, two strategies have been used to improve the efficiency of mucosal drug delivery through the preparation of mucoadhesive and mucus-penetrating nanoparticles. Thiolated silica nanoparticles have been synthesised using 3-mercaptopropyltrimethoxysilane and functionalised with either polyethylene glycol (PEG) or poly (2-ethyl-2-oxazoline) (POZ). The sizes of thiolated, PEGylated and POZylated silica nanoparticles were 53±1, 68±1 and 59±1 nm, respectively. The particle size of both thiolated and POZylated nanoparticles significantly increased at pH≤2, whereas no particle size change was observed at pH 2.5-9 for both these two types of nanoparticles. On the other hand, the size of PEGylated nanoparticles did not change over the studied pH range (1.5-9). Thiolated nanoparticles were more mucoadhesive in the rat small intestine than both PEGylated and POZylated nanoparticles. This may indirectly indicate the mucus-penetrative properties of both PEGylated and POZylated nanoparticles. Each of these nanoparticles has potential applications in mucosal drug delivery.

Biography

W Daear is a PhD Candidate at the University of Calgary. She has a Bachelor’s degree in Biological Sciences with a minor in Nanoscience. She currently has 3 publications in peer reviewed articles (J. Phys. Chem. B., Colloids Surf. B, and Biochim. Biophys. Acta, Biomember).

Abstract

The pulmonary route offers many advantages for drug delivery such as the high surface area and the close proximity to the blood circulation. The air-blood barrier of the alveoli in the lungs is around 500 nm thick. Above the epithelium cells of the alveoli lies a thin aqueous layer with a thickness of 50-80 nm. A monolayer of phospholipids, natural lipids and few proteins called the lung surfactant (LS) adsorbs onto this aqueous film. The major phospholipid classes include phosphatidylcholines and phosphatidylglycerols. One of the main roles of the LS is to reduce the surface tension experienced in the lungs during breathing cycles in order to prevent lung collapse. From the perspective of pulmonary drug delivery, the LS is the first point of interaction for the drug carriers. With the advancements of nanomedicine, nanoparticles (NPs) became highly relevant as novel drug delivery systems. In particular, there is a great scientific interest for the use of biodegradable NPs for the pulmonary delivery route. The objective of our work is to develop a biomimetic model of the LS and study the effects upon interaction with NPs. Therefore, we focus on understanding the mechanism of interaction between biodegradable polymeric NPs with the biomimetic model of the LS and test whether the stability and lateral architecture of LS is affected.  These measurements are done by using Langmuir monolayers at the air-water interface and imaged using Brewster angle microscopy. Results show that the film stability upon compression is not affected, but there are significant changes in the lateral domain organization of the LS upon NP addition. This work is significant because it helps understand the mechanism of NP-LS interaction and will provide an in-vitro screening approach to assess nanotoxicology.

Biography

Seyed Mohammad Mahdi Dadfar has completed his Bachelor and Master of Science at Tehran University and Shiraz University, respectively, both top-tier universities in Iran. He is pursuing his PhD at Karlsruhe Institute of Technology (KIT), Institute of Nanotechnology (INT) under supervision of PD Dr. Michael Hirtz and Prof. Dr. Annie Powell. His PhD project is about functionalized diamond optomechanical circuits for infrared spectroscopy and site-specific gas sensing applications. He is a Member of Iran’s National Elites Foundation (The highest prestige and professional nation foundation for supporting elites). Mahdi Dadfar has published more than 10 papers in reputed journals, holds two national patents and recently has submitted another paper during his PhD. 

Abstract

Different types of click chemistry reactions have been proposed and used for the functionalization of surfaces and materials, and covalent attachment of organic molecules. In the present work, we present and compare two different catalyst-free click approaches, namely azide-alkyne and thiol-alkyne click chemistry, for the generation of nanobiosensors suitable for protein detection. For this purpose, we first functionalized the surface of glass with dibenzocyclooctyne-acid (DBCO-acid), a cyclooctyne with a carboxyl group. Then, the DBCO-terminated surfaces were functionalized with different fluorescent and nonfluorescent azide and thiol inks via microchannel cantilevers spotting (µCP) (Figure 1). Click reactions were performed at different temperatures and times and the optimum conditions of 37 °C/20 min and 37°C/40 min was found for azide-alkyne and thiol-alkyne reactions, respectively. Although, due to no need for catalysts or additional additives, mild reaction conditions, and high reaction rate, both routes worked reliable for surface functionalization, the protein binding experiments revealed that using a thiol-alkyne route will obtain the highest surface density of molecular immobilization in such spotting approaches. The obtained achievements and results from the protein binding experiments with streptavidin proved the potential for application of these microarrays in manufacturing nanobiosensors for protein detection and other biomedical/biological applications.