Pharmaceutical Nanotechnology and Nanomedicine 2018-04-18 London ,UK

Xudong Huang has completed his PhD from MIT and postdoctoral studies at Massachusetts General Hospital and Harvard Medical School. He is the Co-Director of Neurochemistry Lab, Psychiatry Department of Massachusetts General Hospital. He has published more than 90 papers in reputed journals. He is the Editor- in-Chief for International Journal of Biomedical Nanoscience and Nanotechnology, and has been serving as an editorial board member of repute.

Alzheimer’s disease (AD) has become a pandemic due to our nation’s burgeoning aging population. A membrane embedded aspartyl protease complex with presenilin as the catalytic component- γ-secretase and β-site aspartyl cleaving enzyme (BACE1) or β-secretase are responsible for synergistic proteolytic cleavages of amyloid precursor protein (APP) and ultimate generation of amyloid Aβ peptides in AD patients’ brain. Their inhibition and modulation have been proposed as therapeutic strategies for AD. Nevertheless, BACE1 knockout mice have phenotypes such as sensorimotor impairments, spatial memory deficits, and displayed seizures. On the other hand, lysosomal aspartyl protease- cathepsin D (CatD) is down regulated at both transcriptional and translational level and its processing is altered in AD fibroblasts. Thus, both BACE1 and CatD have been suggested as potential AD biomarkers. Hence, we intend to develop in vivo smart probes targeting BACE1 and CatD as they may be tools for the preclinical and even clinical development of AD therapy and diagnosis. To achieve this goal, we have created a multi-wavelength molecular imaging probe to report on the simultaneous activities of cathepsin D (CatD) and BACE1, and validated this probe with pure enzyme mixtures and cell lines. Magnetofluorescent nanoparticles (crosslinked dextran iron oxide nanoparticles or CLIO) served as a starting material. Peptide substrates containing a terminal nearinfrared (NIR) fluorochrome (a fluorophore emitting at 688 nm for CatD or a fluorophore emitting at 775 nm for BACE1) were conjugated to the CLIO nanoparticles. The CatD substrate contained a phenylalanine-phenylalanine cleavage site more specific to CatD than BACE1. The BACE1 substrate contained the sequence surrounding the leucine-asparagine cleavage site of BACE1 found in APP, which is more specific to BACE1 than CatD. The nanoparticles were purified by gel filtration and their fluorescence intensities were determined using a fluorescence plate reader. The CatD nanoparticle demonstrated a 17-fold increase in fluorescence when incubated with CatD, approximately 3 times higher in fluorescence than BACE1. The BACE1 probe exhibited a 8-fold increase in fluorescence when incubated with BACE1, approximately 2 times higher in fluorescence than CatD. Probe specificity was also demonstrated in the human SH-SY5Y cells, in which the probe monitored enzymatic cleavage. In the SH-SY5Y cells, there was a 6-fold increase in CatD fluorescence as well as a 2-fold increase in BACE1

fluorescence. We conclude that this novel molecular imaging probe with a dual NIR fluorochrome can detect both BACE1 and CatD enzymatic activities selectively in either pure enzyme mixtures or cell lines, demonstrating its potential utility as a tool for development of AD therapy and diagnosis.

Xudong Huang has completed his PhD from MIT and postdoctoral studies at Massachusetts General Hospital and Harvard Medical School. He is the Co-Director of Neurochemistry Lab, Psychiatry Department of Massachusetts General Hospital. He has published more than 90 papers in reputed journals. He is the Editor- in-Chief for International Journal of Biomedical Nanoscience and Nanotechnology, and has been serving as an editorial board member of repute.

Alzheimer’s disease (AD) has become a pandemic due to our nation’s burgeoning aging population. A membrane embedded aspartyl protease complex with presenilin as the catalytic component- γ-secretase and β-site aspartyl cleaving enzyme (BACE1) or β-secretase are responsible for synergistic proteolytic cleavages of amyloid precursor protein (APP) and ultimate generation of amyloid Aβ peptides in AD patients’ brain. Their inhibition and modulation have been proposed as therapeutic strategies for AD. Nevertheless, BACE1 knockout mice have phenotypes such as sensorimotor impairments, spatial memory deficits, and displayed seizures. On the other hand, lysosomal aspartyl protease- cathepsin D (CatD) is down regulated at both transcriptional and translational level and its processing is altered in AD fibroblasts. Thus, both BACE1 and CatD have been suggested as potential AD biomarkers. Hence, we intend to develop in vivo smart probes targeting BACE1 and CatD as they may be tools for the preclinical and even clinical development of AD therapy and diagnosis. To achieve this goal, we have created a multi-wavelength molecular imaging probe to report on the simultaneous activities of cathepsin D (CatD) and BACE1, and validated this probe with pure enzyme mixtures and cell lines. Magnetofluorescent nanoparticles (crosslinked dextran iron oxide nanoparticles or CLIO) served as a starting material. Peptide substrates containing a terminal nearinfrared (NIR) fluorochrome (a fluorophore emitting at 688 nm for CatD or a fluorophore emitting at 775 nm for BACE1) were conjugated to the CLIO nanoparticles. The CatD substrate contained a phenylalanine-phenylalanine cleavage site more specific to CatD than BACE1. The BACE1 substrate contained the sequence surrounding the leucine-asparagine cleavage site of BACE1 found in APP, which is more specific to BACE1 than CatD. The nanoparticles were purified by gel filtration and their fluorescence intensities were determined using a fluorescence plate reader. The CatD nanoparticle demonstrated a 17-fold increase in fluorescence when incubated with CatD, approximately 3 times higher in fluorescence than BACE1. The BACE1 probe exhibited a 8-fold increase in fluorescence when incubated with BACE1, approximately 2 times higher in fluorescence than CatD. Probe specificity was also demonstrated in the human SH-SY5Y cells, in which the probe monitored enzymatic cleavage. In the SH-SY5Y cells, there was a 6-fold increase in CatD fluorescence as well as a 2-fold increase in BACE1 fluorescence. We conclude that this novel molecular imaging probe with a dual NIR fluorochrome can detect both BACE1 and CatD enzymatic activities selectively in either pure enzyme mixtures or cell lines, demonstrating its potential utility as a tool for development of AD therapy and diagnosis.

Dae Joon Kang is a Professor at Physics Department of Sungkuynkwan University, one of the premiere research-oriented universities in Korea. He has published more than 180 SCI peer-reviewed articles in the top journals including Nature Nanotechnology, Advanced Materials, Nano Letters, ACS Nano, Advanced Functional Materials and several book chapters in solid-state physics and nanotechnology areas covering from nanofabrication to materials synthesis and to device physics. The quality of his work can be easily indicated by Scopus H-index of 40 and the total citation of over 5000. He has served as an Editorial Board Member for several internationally renowned scientific journals including a section editor for IOP journal “Nanotechnology” since 2006 and an Editor-in-Chief for Current Nanoscience since 2014.

Transfer and integration of nanostructures onto desirable substrates is the prerequisite for their fundamental studies and practical applications. Conventional transfer techniques involving stamping, lift-off and/or striping are greatly limited by the process-specific shortcomings, including the requirement for chemical etchant or high-temperature annealing and the introduction of surface discontinuity and/or contamination that can greatly deteriorate the intrinsic properties of the transferred materials. We have developed a universal transfer method implementable at mild conditions to transfer large area 2-Dimensional (2D) materials grown by chemical vapor deposition method onto various substrates. This technique not only allows the effective transfer to an arbitrary target substrate with a high degree of freedom, but also avoids PMMA etching thereby maintaining the high quality of the transferred 2D materials with minimum contamination. We applied this method to transfer various 2D materials grown on different rigid substrates of general interest, such as graphene on copper foil, h-BN on platinum and MoS2 on SiO2/Si. We believe that our method can facilitate the development of nanoelectronics by accelerating the clean transfer and integration of low-dimensional materials into multidimensional structures.

Istvan Toth is the Chair in Biological Chemistry and Professor of Pharmacy in the University of Queensland (UQ), Brisbane, Australia; Affiliated Professorial Research Fellow and Group Leader, Institute of Molecular Biosciences, UQ. He has graduated with a degree in Chemical Engineering from the Technical University, Budapest, Hungary in 1969 and was awarded with PhD in 1972 for research in Alkaloid Chemistry. In 1994, he was awarded a DSc for his work on Drug Delivery. He is an elected RACI Fellow, Fellow of the Queensland Academy of Arts and Sciences and Fellow (External) of the Hungarian Academy of Sciences. He has over 400 peer-reviewed publications (>500 citations/year since 2012), 44 patents, and a strong record in research commercialization.

We have developed an oral vaccine delivery system to prevent infection by Group A Streptococcus (GAS) by encapsulating lipid core peptide (LCP) antigens into the liposomes. We synthesized the LCP construct by attaching C-16 lipoamino acid (Toll-like receptor 2 agonist) to J-14 (B-cell epitope derived from GAS M-protein) and P25 (CD4+ T helper cell epitope). Blank liposomes were formulated and optimized for charge and lipid content using a thin film formation method. Optimized liposomes were coated with positively charged trimethyl chitosan (TMC) then negatively charged sodium alginate in a layerby- layer approach. These formulations were subsequently characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Optimized formulations were further investigated for their efficiency of uptake by intestinal immune cells and ability to induce mucosal IgA and systemic IgG responses. Fertility is controlled by decreasing the level of circulating Gonadotropin-Releasing Hormone (GnRH) or stimulating the down-regulation of GnRH receptors on gonadotropin cells. Using two independent approaches we regulated the action of GnRH on gonadotropic cells, thereby controlling fertility in mice and ram models. The first approach was to develop super-agonist by modifying GnRH with lipids and sugars, the second approach was immunocastration.

May M Alrashed has completed his/her PhD in Molecular Genetics. She is serving as Vice Dean for the College of Applied Medical Sciences, King Saud University and Assistant Professor at the Department of Clinical Laboratory Sciences. She is the Cofounder of Zahra Breast Cancer Association. Her research interests include molecular characterization of different diseases, mutation identification, whole exome sequencing, next generation sequencing and nano technology.

An antibiotic-resistant bacterium is a problem around the world. Silver nanoparticles (AgNPs) seem to be a potential candidate for development of new antimicrobial agents. In this study, disc diffusion methods and PCR were used for phenotypic and molecular characterization of extended spectrum β-lactamase and carbapenemases producing E.coli and Klebsiella pneumoniae clinical isolates. Antibacterial activity of chemically and green synthesized AgNPs were measured using micro broth dilution method, and genotoxicity of AgNPs was evaluated using Comet Assay. Molecular characterization revealed the dominance of CTX-M-15 and NDM-1 resistance genes. Both types of silver nanoparticles show a bactericidal effect against all isolates. The efficiency of green synthesized AgNPs was significantly better than chemically synthesized particles while bacterial DNA damage produced by chemically synthesized AgNPs was greater than green synthesized AgNPs. These results suggest the superiority of green synthesized AgNPs as a safer antibiotic alternative.

Bonex Wakufwa Mwakikunga has his patent on the lateral-gate field effect transistor with drain-source inter-digitation (coined LaGIDDS-FET) granted in the USA (2017), China (2017) and South Africa (2016) after rigorous PCT reviews. He also has more than 100 publications in impactful journals, a basketful of PhD and MSc students graduated under him and technology demonstrations apart from having guided some of his colleagues now to being top researchers in CSIR and beyond. He conducts research on nano-materials and develops nano-devices for gas sensing, breath analysis and nano-lasing applications. This is to answer the call for monitoring of gas pollutants in the mines, environment and health sectors including nano-laser-based data communication/computing systems. His research interests have seeded large-funding-attractors such as the Nano-Micro Device Manufacturing Facility and the gas sensing programme.

The present technology proposes a competitive solution in diagnosis of diabetes mellitus through exhaled breath. It is well known that acetone in human breath can be a biomarker and indicator of fasting and/or lack of insulin in the blood. In the present technology, a patented micro-nano-chip (Grant # US 9683957) is packaged around the pertinent electronics in order to present a complete device for diagnosis and routine monitoring glucose levels. The new solution is non-invasive and hence alleviates pain as well as opportunistic infection which lead to currently more than 2 million amputations per year worldwide. From the tests conducted on one patient for the months of November 2014 to January 2015 in a home with a type 1 diabetes patient, the present technology has been used to correlate its responses to human breath to the many parameters found in blood of such a patient. There is a positive correlation of between 94% to about 97% depending on whether the readings were taken in the afternoon or morning and whether it is pre-fasting or post-fasting period. The technology trademarked here as MAL4NanoSnifferTM can be presented as an alternative solution, among a few competitors, to the diagnosis of glucose levels in diabetes patients. The technology can easily be extended to diagnosis of other diseases such as lung cancer and renal failure.

The paper also includes calibration efforts to have the analyzer to convert acetone responses into blood glucose taking into account humidity, temperature and pressure. Discussions on the role of gate voltage on the enhancement of the recovery rate of the nano-sensors are also included.

Jyh-Ping Chen has been a Professor in Chemical and Materials Engineering at Chang Gung University since 1997. He is currently a Researcher at the Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital and holds joint appointments as Professor in the Department of Materials Engineering, Ming Chi University of Technology, and Research Center for Food and Cosmetic Safety and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Taiwan, ROC. He has received his BS degree in Chemical Engineering from National Taiwan University in 1981 and PhD in Chemical Engineering from Pennsylvania State University in 1988. He has published over 150 papers in SCI journals with more than 3500 citations. He is a Guest Editor or Editorial Board Member for 12 international journals and a peer reviewer for more than 50 reputed SCI journals. His current research interests include biomaterials, tissue engineering and drug delivery.

Wound healing is a complex process involving many interdependent and overlapping sequences of physiological actions. Ideal wound dressings can replace native skin functions in full thickness skin wounds through faster healing rate and also by reducing scar formation. The application of exogenous lactate released from poly(lactic-co-glycolic acid) (PLGA) polymer accelerates angiogenesis and the wound healing processes. Several in vitro and in vivo studies have demonstrated the effectiveness of curcumin in decreasing the release of inflammatory cytokines, inhibiting enzymes associated with inflammations, and scavenging free radicals that is the major cause of inflammation during wound healing. Heparin has binding affinities to various growth factors. With the unique and beneficial features offered by those molecules toward the complex process of wound healing, we postulate a composite wound dressing constructed from PLGA, curcumin and heparin would be a good candidate to accelerate scarless wound healing. In this work, we use electrospinning to prepare curcuminloaded aligned PLGA nanofibrous membranes (PC NFMs). PC NFMs were further subject to oxygen plasma modification and surfaced-grafted with heparin through carbodiimide-mediated covalent bond formation to prepare curcumin-loaded PLGA-g-heparin (PCH) NFMs. The nanofibrous membranes could act as three-dimensional scaffolds to attract fibroblast migration, reduce inflammation, and increase wound-healing related growth factors concentrations at wound sites. From scanning electron microscopy analysis, the nanofibers in each NFM are with diameters ranging from 456 to 479nm and with alignment angles within ±0.5°. The NFMs show high tensile strength and good water absorptivity and provide suitable pore size for nutrients/wastes transport. Exposure of human dermal fibroblasts to the extraction medium of PC or PCH NFM showed significant protective effects against hydrogen peroxide than PLGA NFM. In vitro wound healing assays also showed that the extraction medium of PCH NFM showed significantly better migration ability toward fibroblasts than PC NFM, which is further better than PLGA NFM. The in vivo healing efficiency of the NFMs was further evaluated by a full thickness excisional wound healing diabetic rat model. After 14 days, PCH NFMs exhibits 86% wound closure rate, which is significantly different from other groups (79% for PC and 73% for PLGA NFM). Real-time PCR analysis indicated PC and PCH NFMs down regulated anti-oxidative enzymes like glutathione peroxidase (GPx) and superoxide dismutase (SOD), which are wellknown transcription factors involved in cellular inflammatory responses to stimuli. From histology, the wound area treated with PCH NFMs showed more vascular lumen formation from immunohistochemistry of α-smooth muscle actin. The wound site also had more collagen type III (65.8%) expression and less collagen type I (3.5%) expression, indicating scar-less wound healing. From Western blot analysis, the PCH NFM showed good affinity toward growth factors from increased concentration of transforming growth factor-β (TGF-β) and fibroblast growth factor-2 (FGF-2) at the wound site to accelerate wound healing. From the results, we suggest PCH NFM as a promising candidate for wound dressing applications.

Toyoko Imae is the Honorary Chair Professor of National Taiwan University of Science and Technology, Taiwan. She has joined there immediately after retiring from Keio University, Japan. She is also a Professor Emeritus of Nagoya University, Japan, since 2006. Her recent research target is “Nanoarchitecture and Nanotechnology” towards energy, environmental and biomedical sciences. She has published 319 journal articles, 25 reviews, 20 patents, 27 book chapters and 4 edited books. She has been conferred several awards as represented by Award of Ministry of Environment. She also contributes to the academic advancement as a President of Asian Society for Colloid and Surface Science since 2013

The attainment of carbon-free society and, therefore, the development of renewable energy are most significant issues in the current days. The composite systems consisting of multiple components sometimes compensate their defects each other and/ or enhance synergistically their characteristics. In this talk, I report the fabrication of nanocomposites made from components with different properties like carbon materials, polymers and metal nanoparticles. Successively, these nanocomposites are applied to green chemistry. Cellulose nanofibers are one of typical renewable materials. Since the functionalized cellulose nanofibers are nanometer-sized, they can form fine films embedded functional materials. They were functionalized for photoinduced enzyme reaction by attaching poly (amido amine) dendrimer, photosensitizer and enzymes. As-prepared system effectively worked for CO2 capture and decomposition to methanol. Thus, this system could act both for the low carbon and the solar fuel production. With the propagation of electric car, there have been challenged to the discovering of the sustainable, clean and environmentally-friendly fuels. Hereupon, hydrogen is an inspiring alternative fuel and energy carrier, being free from CO2 emission. The successful attaining of hydrogen production from the electrocatalytic hydrogen evolution reaction was kept by using electrocatalyst systems containing ~1 wt% of platinum nanoparticles protected by dendrimer. Supercapacitors are one of the most talented devices for energy storage. They must exhibit many advantages, including high energy density, fast charge/discharge rate and excellent durability. Thus, we report materials of the non-faradic carbon-based electric double layer

capacitors and the faradic pseudocapacitors. The obtained composites displayed a synergetic capacitance performance and excellent charge/discharge properties.