Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 25th Nano Congress for Future Advancements Dublin, Ireland.

Day 1 :

Keynote Forum

Oliver G. Schmidt

Institute for Integrative Nanosciences, Germany

Keynote: Microtubular nanomembrane devices: From energy storage to reproduction technologies

Time : 09:30 - 10:00

Conference Series Nano Congress 2018 International Conference Keynote Speaker Oliver G. Schmidt photo
Biography:

Oliver G. Schmidt is the Director of the Institute for Integrative Nanosciences at the Leibniz IFW Dresden, Germany. His interests bridge across several disciplines, ranging from nanomaterials and nanoelectronics to microfluidics, microrobotics and  biomedical applications. He has received several awards: the Otto-Hahn Medal from the Max-Planck-Society in 2000, the Philip-Morris Research Award in 2002, the Carus-Medal from the German Academy of Natural Scientists Leopoldina in 2005, and the International Dresden Barkhausen Award in 2013. Most recently, he was awarded the Gottfried Wilhelm Leibniz-Prize 2018 of the German Research Foundation. The Leibniz-Prize is Germany’s most important research award and recognizes his outstanding work in the investigation, manufacturing and innovative application of functional nanostructures.

 

 

Abstract:

Microtubular nanomembrane devices (MNDs) with outstanding properties are self-assembled into fully functional and integrative three-dimensional architectures. This makes them attractive for a broad range of applications and scientific research fields ranging from energy storage to reproduction technologies. MNDs are used to construct ultra-compact energy storage devices as well as ultra-sensitive advanced electronic circuitry, nanophotonic cavities, sensors and optofluidic components towards the implementation of a lab-in-a-tube system. They are also useful to study basic mechanisms of single cancer and stem cell migration, growth and mitosis in realistic 3D confined environments.  Off-chip applications include biomimetic microelectronics for regenerative cuff implants and the development of hybrid microbiorobotic motors for paradigm shifting reproduction technologies. Cellular cyborg machinery is put forth for novel schemes in targeted drug delivery and cancer treatment.

 

Conference Series Nano Congress 2018 International Conference Keynote Speaker Rongjun Chen photo
Biography:

Rongjun Chen obtained his MSc Degree in Materials Science from Tsinghua University (P R China) in 2003; pursued PhD Degree at Cambridge University (UK) during the period 2003-2007, with focus on polymer drug delivery. He carried out his Postdoctoral Research at Cambridge University first on lyophilisation of pharmaceuticals and then on manufacture of clinical-grade lentiviral vectors for gene therapy during the period October 2006 to September 2009. In May 2013, he moved to Imperial College London as a Lecturer and is currently a Senior Lecturer since 2016. From October 2009 to April 2013, he started his independent academic career by taking a tenure-track faculty position as the Group Leader and BHRC Senior Translational Research Fellow at the University of Leeds. His research interests focuses on biomaterials, nanomedicine, drug delivery and cell therapy.

 

Abstract:

It remains a major challenge to effectively deliver therapeutic agents, in particular macromolecules, through negatively charged lipid membrane barriers. It is the most limiting step preventing successful implementation of macromolecule-based cell modification and intracellular therapies. This is due to endosomal entrapment of macromolecules and their degradation in lysosomes. Many researchers have used cationic delivery systems to address this challenge. However, the positive charge could cause some issues, such as unfavorable biodistribution, rapid renal clearance and high non-specific cytotoxicity. This presentation presents an alternative delivery strategy based on an anionic drug delivery platform. It covers our recent efforts on design and synthesis of novel anionic, viral-peptide-mimicking, pH-responsive, metabolite-derived polymers, and evaluation of their use in intracellular drug delivery in vitro and in vivo. Strict control over the size, structure, hydrophobicity-hydrophilicity balance and sequence of the polymers can effectively manipulate interactions with lipid membrane, cell and tissue models. It has been demonstrated that the biomimetic polymers can successfully traverse the extracellular matrix in three-dimensional multicellular spheroids, and also enable efficient loading of a wide range of macromolecules into the cell interior. This can represent a versatile delivery platform, suitable for targeted therapeutic delivery and cell therapy for treatment of various diseases including but not limited to cancer.

 

Conference Series Nano Congress 2018 International Conference Keynote Speaker Andrew David Miller photo
Biography:

Andrew D Miller is well known as a leading Chemist Expert in the understanding and exploitation of molecular mechanisms in biology. The overall goal of his academic research has been and continues to be the design and creation of advanced therapeutics and diagnostics that address unmet medical need in the treatment of chronic diseases (such as cancer, diabetes, pain and some infectious diseases). From 1990-2010, he was a Member of academic staff in the Chemistry Department of Imperial College London (UK) where he founded the Imperial College Genetic Therapies Centre (GTC) in 1998, and became Full Professor of Organic Chemistry and Chemical Biology in 2002. Since 2010, he has been affiliated with King’s College London (UK) and more recently with the Veterinary Research Institute (VRI) in Brno, Czech Republic, where he is the Director of OPVVV Project FIT and its Key Foreign Scientist (KFS). He Co-Founded KP Therapeutics Ltd in 2016 with a pipeline of Precision Therapeutic Approaches (PTAs) in discovery & development for the diagnosis and treatment of chronic diseases. He has currently published nearly 250 papers, book chapters and alike, including at least 26 patents and patent applications. He is also Principal Writer of the first textbook of chemical biology (“Essentials of Chemical Biology”, John Wiley & Sons.

 

Abstract:

Precision Medicine is considered by many to be a necessary future for the treatment for all diseases. Fundamentally, this can be divided into two subsections, namely personalized medicine and precision therapeutics. With personalized medicine, the aim is to understand the genetic, immunological and/or metabolic individuality of patients in order to match individual patients with the most appropriate active pharmaceutical ingredients (APIs) for treatment of their particular disease(s). With precision therapeutics, the aim is to take control of the delivery of APIs to disease target tissue, by means of nanomedicine, and/or make use of select APIs that have extreme target specificity. The focus of this lecture is in precision therapeutics, as demonstrated by four worked examples of precision therapeutic approaches (PTAs) that are currently being taken forward in my laboratories and the laboratories of key collaborators for the treatment of chronic diseases. The chronic diseases of interest are chronic pain, epilepsy, cancer, non-alcoholic fatty liver disease (NAFLD) /diabetes type II, and infectious diseases such as influenza, Zika virus and HIV. By way of example, the right-hand side panel outlines a PTA for the treatment of cancer. In effect, a combination of bio-imaging and the application of image-guided targeting enable anti-cancer drug delivery nanoparticles to accumulate in a tumour lesion of choice and no obvious place elsewhere in the body. Accumulated nanoparticles may then release these anti-cancer drugs for local activity against tumour tissue saving other body tissues from unwanted exposure to these otherwise cytotoxic drugs. Implementation of such a PTA in the clinic could radically improve patient chemotherapy outcomes whilst reducing both required drug doses and side effects to an unprecedented degree. Such potential step changes in disease treatment explain why precision therapeutics should be an indispensable part of future medicine.

 

  • Plenary Session
Speaker
Biography:

Animesh Jha is Professor of Applied Materials Science with special research interest in glass based and nano-scale materials, photonic materials, laser gain medium engineering and laser-matter interaction. He obtained his Bachelor and Master of Engineering Degrees in Metallurgy from the University of Roorkee (UP, India) and the Indian Institute of Science Bangalore (India) in 1979 and 1981, respectively. In 1981, he joined the Imperial College of Science & Technology, London for his PhD in thermodynamics of sulphide minerals for metal processing, and acquired significant interest in heterogeneous chemical reaction kinetics and multiphase equilibria. After finishing PhD in Oct 1984, he pursued his interest in the area of phase equilibrium and transformation kinetics in metallic and inorganic glasses as a post-doctoral research fellow at the University of Sheffield (UK) until April 1989, after which he was appointed as a lecturer at Brunel University in Uxbridge (UK). In March 1996 he joined the University of Leeds (Leeds, UK) as a Reader where he has been undertaking original research in nanoscience approaches for bio-materials, glass engineering and 2D-materials technology for device engineering. AJ became Professor in Aug 2000. He is author of more than 400 research papers and has also written a book on “Inorganic Glasses for Photonics” which was published in 2016. He is also inventor/co-inventor on more than 45 patents. AJ was awarded the Fellowships of Institute of Physics (London) and the Royal Society of Chemistry in 2010 and 2016, respectively. He has also won innovation awards (SMART, Yorkshire Concept) for technological demonstration of advanced glasses and fibres for lasers and amplifiers, and their applications. He is actively involved in PhD and PDRF training and promotes emerging scientists in achieving career goals via Marie-Curie and other prestigious Fellowship schemes.

 

Abstract:

Dental enamel is acellular and avascular mineralized tissue with more than 95% mineral content. Although, the underlying softer dentine is connected with the microvasculature via the soft tissue therefore, possesses intrinsic regenerative capacity for mineralization which lacks in the enamel tissue. Consequently, the oral acid induced erosive damage on enamel is irreversible, and leads to lesion formation. Unattended lesion may lead to hypersensitivity and feeling of pain. Advanced stage of eroded enamel with symptoms of hypersensitivity might lead to tooth loss in adults. Traditional clinical strategies for the repair of acid-eroded enamel include the use of BIS-GMA polymeric materials which has incompatible mechanical properties with the adjoining hard minerals, and this type of bonding leads to failure of restored enamel area in a challenging oral environment. Modern toothpastes provide temporary relief from hypersensitivity; however, there is no long-term solution for treating early stages of acid erosion which may lead to sensitive teeth. Another condition, which affects especially the ageing population, is the tooth wear, which leads to tooth thinning and weakening in the lingual areas of mouth. Rebuilding the entire damaged tissue region remains a challenge. In the absence of any intrinsic regenerative means of restoring damaged tissue, our proposal focusses on developing a novel exogenous tissue re-engineering methodology, in which the mineralization of tooth surface involves: i) application of nano- and amorphous iron-calcium phosphate minerals (e.g. hydroxyapatite, fluorapatite and brushite) in the form of colloidal paste; which is then ii) bonded with the surrounding healthy enamel by irradiating with a femtosecond pulsed near-IR laser. The presence of a homogeneous dispersion of nano-scale of iron oxide in the calcium-iron phosphate matrix acts as resonant antennae for absorbing near-IR pulsed laser radiation, and helps in the dispersion of thermal energy uniformly in the irradiated region without causing damaged to the healthy tissue. The two steps (i) and (ii) are illustrated in Figure 1. The mechanisms of phase transformation and dissipation have been analyzed for different irradiation conditions (e.g. at 1040 nm wavelength, 1 GHz repetition rate and 0.4 W average power), and the resulting phase transformation is compared for understanding the bonding and potential radiation induced damage mechanisms including ablation, thermal and toxicity effects. Potential opportunity for micro-surgical device engineering is discussed for ultimate clinical use. The mechanical properties including brushing trials on restored surfaces of bovine enamels are also reported.

 

Speaker
Biography:

Han Yong Jeon is an Geosynthetics/Technical Organic Materials Researcher and he was the 32nd President of Korean Fiber Society during 2014-2015. He has published more than 843 papers in domestic and international conferences. He wrote 20 texts including 'GEOSYNTHETICS’ and also published 143 papers in domestic and international journals. He has awards of Marquis Who's Who-Science and Engineering in 2003-2017 and also, he got the 33rd Academy Award of Korean Fiber Society in 2006 and Excellent Paper Award of 2012 by The Korean Federation of Science and Technology Societies.     

Abstract:

Melt-blending method was performed to make nano fibers which have excellent properties of liquid crystal polymer(LCP). If nano fiber is manufactured depending on LCP, there is every possibility of utilizing in a higher value-added industry. Although there are some processes to produce nano fiber such as electrical spinning and sea-island fiber by conjugate spinning etc., it still has difficulties that electrical spinning has a low output and sea-island fiber by conjugate spinning using specified nozzle is restricted to reduce fiber diameter. It will be effective to solve the existing problems as mentioned above if to control of fibrillation shape is able to make a consecutive fiber morphology through spinning process. The research that deal with making continuity through the way to regulate size of fibril by sea-isaland fiber formation has not yet been achieved in existing dissertations of manufacturing of fibers related to spinning fibrillation method. This study is planned to verify control of sea-island fiber formation via study of its behaviors that are influenced by LCP and poly(ethylene terephthalate) (PET) blend composition and confirms size changes of fibril shape by spinning process. This fibrillation changes show fibril formation and morphology according to the spinning parameters including nozzle and spinning related condition. Distribution of nano fiber fibrillation were observed to LCP and PET blending process for conjugate spinning. Fibrillated fibers of sea-island morpholohy were distributed relatively evenly in the spinning parameters. Also, this phenomenon was assumed that the miscibility of LCP/PET and the flow characteristics correlate with the phenomenon, so conducted the analysis. In this study, effect of LCP/PET blending and spinning parameters on sea-island fibrillation to make nano fibers was investigated through morphological and crystallographical analysis.

 

Speaker
Biography:

He is researcher from 2000. He have completed PhD in 2008 from Nara Women’s University and continued postdoctoral studies with Osaka University and Nara educational University. He have published more than 25 papers in reputed journals. He have an interest in iridium complexes and Ruthenium complexes. Recently he also interested  in metal free emission product.

 

Abstract:

A series of metal-free compounds, i.e., bpyHPF6 (1), dmbpyHPF6 (2), phenHPF6 (3) dpphenPF6 (4), bqnHPF6 (5) and ppyHPF6 (7) were newly prepared and characterized by electrospray ionization mass spectrometry, and UV-vis spectroscopy. Abbreviations used are bpy = 2,2’-bipyridine, dmbpy = 4, 4’-dimethyl-2, 2’-bipyridine, phen = 1,10-phenanthroline, bqn = 2,2’-biquinoline and ppy = phenylpyrizine. The x-ray crystal structures of the four compounds 1, 2, 3, 4 5 and 7 were determined. Monoprotonated pyridine rings are hydrogen bonded intramolecularly to the adjacent pyridine ring in compounds 1, 2, 3, 4 and 5. The p-p* absorption bands in the UV region for 1, 2, 3, 4 and 5 in acetonitrile were red-shifted relative to those of the corresponding neutral unprotonated compounds. Density functional theory was applied to interpret the planarity in 1. The attachment of one proton to the one nitrogen in 5 leads to the remarkable emission (F = 0.10). The attachment of one proton to one nitrogen in 4 also gives the large quantum yield.

 

 

Thomas Maurer

University of Technology of Troyes, France

Title: Nanogauges for integration of strain sensors integrated into matter

Time : 12:50-13:20

Speaker
Biography:

Thomas Maurer is Associate Professor at the University of Technology of Troyes. He has been developing a research activity at the interface of nanotechnology, mechanics and optics, which can be designed as mechanoplasmonics. In parallel, he is a member of the action laboratory of excellence executive committee and responsible of the smart sensors scientific work group whose aim is to integrate sensing functionalities into matter.

 

 

Abstract:

For the past twenty years, nano-optics has emerged as a promising research field thanks to huge progress in nanofabrication and offers great technological potential for applications in fields such as biology, medecine or chemistry. Coupling between plasmonic nanoparticles (NPs), well-known as the plasmon ruler equation, was recently investigated by fabricating arrays of NP dimers with various inter-particle distances using e-beam lithography. In this talk, we aim to illustrate how it should be possible to break through frontiers between mechanics and plasmonics in the next future by showing our first results on the use of gold nanogauges for strain investigation as well as recent advances published in the literature. In particular, the opportunity to develop a new generation of color-changing strain sensors will be discussed.

 

Jae-Jin Shim

Yeungnam University, Republic of Korea

Title: Graphene-based nano materials for energy storage and photocatalysis

Time : 14:00 - 14:30

Speaker
Biography:

Jae-Jin Shim received his BS degree from Seoul National University in 1980, MS degree from KAIST in 1982, PhD degree from the University of Texas at Austin in 1990. He has been a Professor in Yeungnam University since 1994 and served as School Chairman and Vice-Dean of Engineering. He was the President of the Korean Society of Clean Technology and Vice President of the Korean Society of Engineering Education. He is the Director of Institute of Clean Technology and Clean Energy Priority Research Center and served as the Chief Editor of  Clean Technology. He has published 150 papers in reputed journals.

 

Abstract:

Nanomaterials have been employed to improve the performance of the energy storage devices (supercapacitor), sensors, and photocatalysts. Especially, oxides and sulfides of transition metals have been getting attention as they have good electrochemical performances. However, their performances are not satisfactory. Various materials such as graphene and carbon nanotubes have studied to enhance the electrochemical properties owing to their large surface area and high electrical conductivity. Synergistic effects from excellent conductivities of graphene and high electrical properties of metal oxides or sulfides have improved the overall electrochemical performances tremendously. Doping of graphene with nitrogen or sulfur, using metal sulfides instead of metal oxides, and using highly porous materials as substrates also contribute towards performance improvement.

 

Kent Peterson

Fluid Imaging Technologies Inc., USA

Title: The use of flow imaging microscopy for nanoparticle analysis in biopharmaceuticals

Time : 14:30 - 15:00

Speaker
Biography:

Kent Peterson is a graduate with an honors from Boston University’s Graduate School of Management, and a Member of American Mensa Society. He has lead Fluid Imaging Technologies since joining as the founder of the firm 12 years ago. The Company has sold over 600 FlowCams in over 52 countries. Ship-based FlowCam systems have also been at work sampling from every ocean in the world. He has served on a number of boards and is active in community affairs. He has also been named Mainebiz Business Leader of the Year. His achievements include: Fluid Imaging Technologies’ Awards and recognitions include, the Governor’s Award for Business Excellence, the SBA New England Exporter of the Year Award, and the Portland Regional Chamber’s Robert R Masterton Award.

 

Abstract:

Flow imaging microscopy has proven to be an important tool for the analysis of subvisible particulates in parenteral drugs. Now, due to the combined resolving power of blue LED light and patented oil immersion technology, flow imaging microscopes can image and analyze particles as small as 300 nm. The ability to detect transparent particles and differentiate them based on morphology yields significantly more detailed and accurate information than can be acquired using common laser diffraction and light obscuration techniques. Along with sophisticated statistical pattern recognition algorithms, these systems can be used to distinguish between different particulate types such as silicon oil, protein aggregates, and air bubbles. This presentation will present the techniques used to accomplish this.

 

 

  • Speaker Session

Session Introduction

Vladimir P Torchilin

CPBN - Northeastern University, USA

Title: Smart combination nanopreparations for cancer: Bringing drugs inside cells and to individual organelles

Time : 16:30 - 16:55

Biography:

Vladimir P Torchilin, PhD, DSc is a University Distinguished Professor of Pharmaceutical Sciences and Director, Center for Pharmaceutical Biotechnology and Nanomedicine of Northeastern University, Boston, USA. His interests include drug delivery and targeting, nanomedicine, multifunctional and stimuli-sensitive pharmaceutical nanocarriers, biomedical polymers, experimental cancer therapy. He has published more than 400 original papers, more than 150 reviews and book chapters, has written and edited 12 books, and holds more than 40 patents. Google Scholar shows more than 52,000 citations of his papers with H-index of 102. He is Editor in Chief of Current Drug Discovery Technologies, Drug Delivery, and OpenNano; Co Editor of Current Pharmaceutical Biotechnology and on the Editorial Boards of many other journals. He received more than $30 M from the governmental and industrial sources in research funding. He has multiple honors and awards and in 2011, Times Higher Education ranked him number 2 among Top World Scientists in Pharmacology for the period of 2000-2010.

 

Abstract:

Tumor therapy, especially in the case of multidrug resistant cancers, could be significantly enhanced by using siRNA down-regulating the production of proteins, which are involved in cancer cell resistance, such as Pgp or survivin. Even better response could be achieved is such siRNA could be delivered to tumors together with chemotherapeutic agent. This task is complicated by low stability of siRNA in biological surrounding. Thus, the delivery system should simultaneously protect siRNA from degradation. We have developed several types of lipid-core polymeric micelles based on PEG-phospholipid or PEI-phospholipid conjugates, which are biologically inert, demonstrate prolonged circulation in the blood and can firmly bind non-modified or reversibly-modified siRNA. Additionally, these nanopreparations can be loaded into their lipidic core with poorly water soluble chemotherapeutic agents, such as paclitaxel or camptothecin. In experiments with cancer cell monolayers, cancer cell 3D spheroids, and in animals with implanted tumors, it was shown that such co-loaded preparations can significantly down-regulate target proteins in cancer cells, enhance drug activity, and reverse multidrug resistance. This is illustrated by the efficient treatment of MDR (multi-drug resistance) cancer cells with combi-nations of siRNA-Pgp or siRNA-survivin stabilized in polymeric mixed mi-celles and doxorubicin, or tariquidar (Pgp inhibitor) and paclitaxel loaded into the same lipo-some or lipid-core polymeric micelle. In order to specifically unload such nanopreparations inside tumors, we made them sensitive to local tumor-specific stimuli, such as lowered pH, hypoxia, or overexpressed certain enzymes, such as matrix metalloproteases. Using pH-, redox-conditions, hypoxia-, or MMP2-sensitive bonds between different components of nanopreparations co-loaded with siRNA and drugs, we were able to make the systems specifically delivering biologically active agents in tumors, which resulted in significantly improved therapeutic response. We have also developed approaches to target individual intracellular organelles to initiate the apoptosis in resistant cancer cells.

 

Biography:

Sergey Suchkov graduated from Astrakhan State Medical University and was awarded with MD; in 1985 maintained his PhD at the I M Sechenov Moscow Medical Academy and in 2001, maintained his Doctor Degree at National Institute of Immunology , Russia. From 1987 through 1989 was a Senior Researcher at Koltzov Institute of Developmental Biology. From 1989 through 1995, he was the Head of the Lab of Clinical Immunology, Helmholtz Eye Research Institute in Moscow. From 1995 through 2004, a Chair of the Department for Clinical Immunology, Moscow Clinical Research Institute (MONIKI). He has been trained at: National Institute of Health; Wills Eye Hospital, Pennsylvania, USA; University of Florida in Gainesville; University of California San Francisco; Johns Hopkins University, Baltimore, MD, USA respectively. He was an Exe Secretary-in-Chief of the Editorial Board, Biomedical Science, an international journal published jointly by the USSR Academy of Sciences and the Royal Society of Chemistry, UK. At present, he is a Chair, Department for Personalized and Translational Medicine, I M Sechenov First Moscow State Medical University. He is a Member of the: New York Academy of Sciences, USA; American Chemical Society (ACS), USA; American Heart Association (AHA), USA; European Association for Predictive, Preventive and Personalized Medicine (EPMA), Belgium; American Association for Research in Vision and Ophthalmology (ARVO); ISER (International Society for Eye Research); Personalized Medicine Coalition (PMC), Washington, USA.

Abstract:

Catalytic Abs (catAbs) are multivalent immunoglobulins (Igs) with a capacity to hydrolyze the antigenic (Ag) substrate. In this sense, proteolytic Abs (Ab-proteases) represent Abs to provide proteolytic effects. Abs against myelin basic protein/MBP with proteolytic activity exhibiting sequence-specific cleavage of MBP are of great value to monitor demyelination whilst in MS. The activity of Ab-proteases was first registered at the subclinical stages 1-2 years prior to the clinical illness. And the activity of the Ab-proteases revealed significant correlation with scales of demyelination and the disability of the patients as well. So, the activity of Ab-proteases and its dynamics tested would confirm a high subclinical and predictive (translational) value of the tools as applicable for personalized monitoring protocols. Of tremendous value are Ab-proteases directly affecting remodeling of tissues with multilevel architectonics (for instance, myelin). By changing sequence specificity one may reach reduction of a density of the negative proteolytic effects within the myelin sheath and thus minimizing scales of demyelination. Ab-proteases can be programmed and re-programmed to suit the needs of the body metabolism or could be designed for the development of new catalysts with no natural counterparts. Further studies are needed to secure artificial or edited Ab-proteases as translational tools of the newest generation to diagnose, to monitor, to control and to treat and rehabilitate MS patients at clinical stages and to prevent the disorder at subclinical stages in persons-at-risks to secure the efficacy of regenerative manipulations.

 

Biography:

Vladimir P Torchilin, PhD, DSc is a University Distinguished Professor of Pharmaceutical Sciences and Director, Center for Pharmaceutical Biotechnology and Nanomedicine of Northeastern University, Boston, USA. His interests include drug delivery and targeting, nanomedicine, multifunctional and stimuli-sensitive pharmaceutical nanocarriers, biomedical polymers, experimental cancer therapy. He has published more than 400 original papers, more than 150 reviews and book chapters, has written and edited 12 books, and holds more than 40 patents. Google Scholar shows more than 52,000 citations of his papers with H-index of 102. He is Editor in Chief of Current Drug Discovery Technologies, Drug Delivery, and OpenNano; Co Editor of Current Pharmaceutical Biotechnology and on the Editorial Boards of many other journals. He received more than $30 M from the governmental and industrial sources in research funding. He has multiple honors and awards and in 2011, Times Higher Education ranked him number 2 among Top World Scientists in Pharmacology for the period of 2000-2010.

 

Abstract:

Tumor therapy, especially in the case of multidrug resistant cancers, could be significantly enhanced by using siRNA down-regulating the production of proteins, which are involved in cancer cell resistance, such as Pgp or survivin. Even better response could be achieved is such siRNA could be delivered to tumors together with chemotherapeutic agent. This task is complicated by low stability of siRNA in biological surrounding. Thus, the delivery system should simultaneously protect siRNA from degradation. We have developed several types of lipid-core polymeric micelles based on PEG-phospholipid or PEI-phospholipid conjugates, which are biologically inert, demonstrate prolonged circulation in the blood and can firmly bind non-modified or reversibly-modified siRNA. Additionally, these nanopreparations can be loaded into their lipidic core with poorly water soluble chemotherapeutic agents, such as paclitaxel or camptothecin. In experiments with cancer cell monolayers, cancer cell 3D spheroids, and in animals with implanted tumors, it was shown that such co-loaded preparations can significantly down-regulate target proteins in cancer cells, enhance drug activity, and reverse multidrug resistance. This is illustrated by the efficient treatment of MDR (multi-drug resistance) cancer cells with combi-nations of siRNA-Pgp or siRNA-survivin stabilized in polymeric mixed mi-celles and doxorubicin, or tariquidar (Pgp inhibitor) and paclitaxel loaded into the same lipo-some or lipid-core polymeric micelle. In order to specifically unload such nanopreparations inside tumors, we made them sensitive to local tumor-specific stimuli, such as lowered pH, hypoxia, or overexpressed certain enzymes, such as matrix metalloproteases. Using pH-, redox-conditions, hypoxia-, or MMP2-sensitive bonds between different components of nanopreparations co-loaded with siRNA and drugs, we were able to make the systems specifically delivering biologically active agents in tumors, which resulted in significantly improved therapeutic response. We have also developed approaches to target individual intracellular organelles to initiate the apoptosis in resistant cancer cells. 

Biography:

Robert k Prud’homme is a professor in the Department of Chemical and Biological Engineering at Princeton University. He is the founding director of the Program in Engineering Biology. His research program focusses on polymer self-assembly applied to drug delivery. The development of Flash NanoPrecipitation (FNP) in his laboratory enabled the encapsulation of poorly soluble drug compounds and oligonucleotides for therapy directed towards cancer, TB, and injections. FNP is a scalable and continuous process that is enables integrated processing and spray drying for low cost oral and aerosol formulations. Under sponsorship by the Bill and Melinda Gates Foundation, the process is being adopted to formulate new compounds coming from TBA, MMV, and DNDi.

Abstract:

The intravenous delivery of composite gel microparticles (cGMPs) offers a platform for localized treatment of lung cancer. We describe a method for fabrication of cGMPs with average diameters of 35 to 100 µm using shear emulsification and microfluidic droplet generation. We characterized the particles and describe the performance of these particles in vivo. Biodistribution of the cGMPs was selective to the lung after intravenous injection and particle clearance from the lung occurred in 7 weeks. One-week biodistribution studies demonstrated that larger, uniform particles produced by microfluidics provided optimal targeting to lung tissue. We demonstrated that highly loaded cGMPs containing a long wavelength fluorophore allow in vivo analysis of particle biodistribution without the need for ex-vivo organ analysis. The release of camptothecin conjugates from the nanopartricles, and thus, gel microparticles, is tuned from minutes to days by altering the polarity of the nanoparticle core.

 

Biography:

Patrick J Sinko is a Pharmacist (BS, Rutgers 1982) and a Pharmaceutical Scientist (PhD, University of Michigan 1988). He joined Rutgers, The State University of New Jersey in 1991 and rose through the academic ranks where he is currently a Distinguished Professor (II) and the Parke-Davis Endowed Chair in Pharmaceutics and Drug Delivery in the Ernest Mario School of Pharmacy. He is the Principal Investigator of an active research laboratory that focuses on biopharmaceutics, pharmaceutical formulations and molecular-, nano- and micro-scale drug delivery with specific applications to the treatment or prevention of HIV/AIDS, breast, brain and lung cancer, chemical terrorism countermeasures. He has received prestigious National Institutes of Health FIRST and MERIT awards and his lab has been continuously funded by the NIH for over 25 years.

 

Abstract:

Ductal carcinoma in situ (DCIS) is a noninvasive breast cancer (BC) with possible microinvasions into the breast stroma. DCIS accounts for more than 16% of new BC diagnoses in women. DCIS progresses to Invasive Ductal Carcinoma (IDC) over time in 39-53% of patients, if left untreated. The vast majority of BC cases originate in the mammary duct. In this presentation, a nanoscale delivery system will be described that utilizes transpapillary delivery to achieve molecularly targeted, pathway-specific therapy in cancerous areas of the mammary duct. Our preliminary results with a nanosuspension of ciclopirox (CPX) in an orthotopic model of BC established the concept that sustained ductal exposure could completely suppress BC occurrence in vivo. For these studies polymeric NPs (nanoparticles) as well as lipid-polymer hybrid (LPH) NPs were the primary delivery vehicles. In order to achieve sustained precision treatment, HER2, transferrin receptor and/or EGFR were targeted using peptide ligands covalently bound to the surface of NPs. Ligand surface densities of 5% and 10% were evaluated and it was found that surface functionalized NPs enhanced binding and uptake into target cells. Cytoxicity was significantly increased with EGFR or TfR targeted NPs as compared to CPX alone or non functionalized CPX-loaded NPs. A synergistic effect was observed when CPX was administered with gedatolisib, a PI3K/Akt/mTOR inhibitor resulting in a dose reduction index of ~6. In addition, the treatments were effective not only in BC cells but also cancer stem-like cells. Our efforts in addition to describing these studies and results, the engineering of the NPs to enhance ductal retention and specificity will also be described.

 

Biography:

Simon C W Richardson is a Founder, Director and CSO at Intracellular Delivery Solutions Ltd, and Reader (Associate Professor) in Membrane Trafficking and Drug Delivery, at the University of Greenwich, UK. The driving theme behind his research is the intracellular delivery of antisense and RNAi to the cytosol. He is currently leading the Cell Biology Research Cluster within the Faculty of Engineering and Science, located at the Medway campus. His lab is currently working with several technologies based upon attenuated virulence factors that have very low in vitro toxicity profiles (and are minimally disruptive to the cell), and very high efficiency intracellular delivery profiles. We are also examining several methodologies to modulate protein stability and intracellular trafficking to aid the oral delivery of vaccines.

 

Abstract:

Many protein toxins have evolved to access a variety of relatively inaccessible intracellular compartments in order to exert virulence. Counted among this number are proteins such as ricin toxin, shiga toxin, diphtheria toxin and anthrax toxin. These proteins display diverse architecture ranging from AB5 to AB configurations and depending upon the specific B chain in question, entertain a number of strategies from direct membrane penetration to utilizing retrograde trafficking pathways to access a plethora of intracellular compartments including the cytosol. Typically the A chain will exhibit catalytic activity proportional to both cellular intoxication and virulence. However given the facile nature of protein recombination, attenuation is relatively simple. Here we describe the ability of attenuated anthrax toxin (ATx) to manipulate endocytic cargo sorting for the purposes of drug delivery, traversing intracellular compartmental boundaries for nucleic acid delivery. We report not only the efficiency with which siRNA and antisense effectors are delivered but also the mechanisms they utilize to traverse the barriers responsible for intracellular compartmentalization. Attenuated Atx:ASO complexes had transfection efficiency approximately equivalent to Nucleofection®. In HeLa cells, at 200 pmol ASO expression of the target gene was 5.4±2.0% relative to an untreated control after 24 h. Using 200 pmol ASOs, Nucleofection® reduced Synt5 expression to 8.1±2.1% after 24 h. PA:LFn-GAL4:ASO transfection of non- or terminally-differentiated THP-1 cells and Vero cells resulted in 35.2±19.1%, 36.4±1.8% and 22.9±6.9% (respectively) target gene expression after treatment with 200 pmol of ASO and demonstrated versatility. Nucleofection® with Stealth RNAi™ siRNA reduced HeLa Synt5 levels to 4.6±6.1% whereas treatment with the PA:LFn-PKR:siRNA resulted in 8.5±3.4% Synt5 expression after 24 h (HeLa cells). These data underscore the tractability of this approach to both antisense and siRNA delivery.