Day 2 :
Keynote Forum
I B Vijayalakshmi
Bangalore Medical College and Research Institute, India
Keynote: Novel method of patent ductus arteriosus closure in preterm neonates with nano-ibuprofen eluting balloon
Time : 09:00-09:40
Biography:
I B Vijayalakshmi is the first to start Pediatric Cardiology in South India. She has won 34 gold medals, My Nightmare Case award twice at PICS. She has 86 publications and has edited four cardiology books.
Abstract:
Background: Patent ductus arteriosus (PDA) occurs frequently in preterm babies (14%). Treating PDA with oral ibuprofen is common. However large PDAs with pump failure, refractive to medical therapy undergo either surgical ligation or device closure, which carry significant inherent morbidity.Aim: Aim of this study is to evaluate, effect of drug eluting balloons coated with inorganic nanoparticles of ibuprofen in rabbits, initially and then in preterm neonates.Methods: In this proposed prospective study, PDA in rabbits is treatment with drug eluting 3X10 mm coronary balloon coated with inorganic nanoparticles of Ibuprofen. Through the femoral vein 4F catheter is passed via the inferior vena cava, right atrium, right ventricle and pulmonary artery. Then PDA is crossed with a Terumo guide wire under fluoroscopy, the drug eluting balloon is positioned in PDA. The balloon is inflated for 3 min to release the ibuprofen nano particles. Slowly, the balloon is deflated over 3 min to demonstrate duct closure by echocardiography. The balloon and guide wire are removed. Serial echocardiograms are performed to assess the efficacy after 6, 12, 24 and 48 hours. The primary outcomes are noted, along with survival without major neonatal morbidity. Finally, histo-pathological studies of ductal tissue are done.Results: The proportion of PDA closure with drug eluting balloon versus oral ibuprofen will be interrogated. The difference between two groups and the P value will be calculated. (using: SPSS- Prism t test).Conclusions: This novel study of balloon coated with inorganic nanoparticles of Ibuprofen in rabbits could be path breaking.
Keynote Forum
Aharon Gedanken
Bar-Ilan University, Isarel
Keynote: Title: Making the hospital a safer place by the sonochemical coating of the textiles with antibacterial nanoparticles
Time : 09:40-10:20
Biography:
Emeritus Prof. Aharon Gedanken obtained his M. Sc. from Bar-Ilan University, and his Ph. D. degree from Tel Aviv University, Israel. After his postdoctoral research at USC in Los Angeles, he returned to Bar-Ilan in 1975 as a senior faculty. He was a visiting scientist at AT&T Bell Laboratories in 1980-8l, 1984, and 1987-88, and at NIDDK, NIH in the summers of 1989, 1990 and 1991. 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 762 per-reviewed manuscripts in international journals, and has applied for 38 Patents. His H-Index is 80. Gedanken has served as the Department chairman as well as the Dean of the Faculty of Exact Sciences at Bar-Ilan University. He is on the editorial boards of 7 international journals. He leads a group of 16 research people. 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 awarded the prize of the Israel Vacuum Society and the Israel Chemical Society for excellence in Research
Abstract:
Sonochemistry is an excellent technique to coat nanomaterials on various substrates, imparting new properties to the substrates. After a short demonstration of coating NPs on ceramics and stainless steel, I'll present the coating of textiles such as polyester, cotton, and nylon. In all cases a homogeneous coating of NPs was achieved. Silver is known for generations as antibacterial, and indeed the Ag NPs have killed the gram-negative E. Coli (strain 1313) as well as the gram-positive Staphylococus aureus (strain 195) bacteria very efficiently. Lately, the FDA shows less enthusiasm towards nanoAg, as a result, we have moved to NPs of ZnO, and CuO as antibacterial agents. They were coated on the above-mentioned fabrics and showed excellent antibacterial properties. The coated textiles were examined for the changes in the mechanical strength of the fabric. A special attention was dedicated to the question whether the NPs are leaching off the fabric when washed repeatedly. The coated ZnO NPs on cotton underwent 65 washing cycles at 92 0 C in water in a Hospital washing machine, no NPs were found in the washing solution and the antibacterial behavior was maintained. Recently, an experiment was conducted at PIGOROV Hospital in Sofia, Bulgaria in which one operation room was equipped with antibacterial textiles, namely, bed sheets, pajamas, pillow covers, and bed covers. 22 Patients in this operation room were probed for bacterial infections. Their infection level was compared with 17 control patient that were using regular textiles. The results are demonstrating that a lower infection level is observed for those patient exposed to the antibacterial textiles. Lately, we have synthesized NPs of a new material, Cu0.89Zn0.11O that kills bacteria 10,000 times better than ZnO or CuO. The mechanism of the killing was studied and will be presented.Coating of Catheters with the above mentioned NPs were performed and the coated catheters were inserted in rabbits. Results showed that the urine of the rabbits was not contaminated with bacteria and the growth of biofilm on the Catheters is avoided.
Keynote Forum
Stoyan Sarg Sargoytchev
World Institute for Scientific Exploration, USA
Keynote: Using the BSM-SG atomic models and their physical properties for modeling and analysis in sub-nano metric scale
Time : 10:20-11:00
Biography:
Stoyan Sarg Sargoytchev has completed his degree of Masters of Electrical Engineering from Technical University in Sofia and PhD in Physics from Bulgarian Academy of Sciences. Currently, he is with the World Institute for Scientific Exploration. He has published more than 70 scientific papers in reputed journals and he is an author of a theoretical monograph BSM-SG.
Abstract:
The BSM-SG atomic models are one of major derivatives of the basic structures of matter super-gravitation unified theory, according to which the near field of atomic nuclei exhibits a space micro-curvature. The re-examination of scattering experiments from this point of view reveals a complex three-dimensional nuclear structure. The effect of space micro-curvature hides the real dimensions of the nuclei, which are with a much larger overall size. Therefore, the coulomb barrier is not as strong as considered by the quantum mechanical models based on the Bohr model of hydrogen. This explains why some nuclear reactions are possible at accessible temperatures. The arrangement of the protons and neutrons in the nuclear structure according to the BSM-SG models matches perfectly the pattern of the periodic table. The nuclear spin also carries a signature of the nuclear configuration and obtains a classical explanation. The reveled structures of BSM-SG atoms and elementary particles exhibit all known quantum mechanical properties while operating with real dimensions. This opens a new opportunity for graphical modeling and analysis in different fields of nanotechnology. The BSM-SG atomic nuclei possess clearly identifiable oxidation numbers and angular directions of the possible chemical bonds. This permits 3D graphical modeling in structural chemistry and biomolecules.
Keynote Forum
Shaker A Mousa
Albany College of Pharmacy and Health Sciences, USA
Keynote: Advanced drug delivery: Nano-targeted delivery for therapeutic and imaging
Time : 11:20-12:00
Biography:
Shaker A Mousa has completed his PhD from Ohio State University, College of Medicine in Columbus and Postdoctoral Fellowship from University of Kentucky in Lexington KY. He also has completed his MBA from Widener University, Chester, PA. He is currently an endowed tenure Professor and Executive Vice-President and Chairman of the Pharmaceutical Research Institute and Vice Provost for Research at ACPHS. He holds over 350 US and International Patents discovering novel anti-angiogenesis strategies, anti-thrombotics, anti-integrins, anti-cancer and non-invasive diagnostic imaging approaches employing various Nanotechnology platforms. He has published more than 1,000 journal articles, book chapters, published patents and books as editor and author. He is a member of several NIH study sections and the Editorial board of several high impact Journals. His research has focused on diagnostics and therapeutics of angiogenesis-related disorders, thrombosis, vascular and cardiovascular diseases.
Abstract:
Targeted delivery of drug incorporated nanoparticles, through conjugation of tumor-specific cell surface markers, such as tumor-specific antibodies or ligands can not only enhance the efficacy of the anticancer drug but also reduce the unwanted toxicity of the drug. Additionally, multifunctional characteristics of the nano-carrier system would allow for simultaneous imaging of tumor mass, targeted drug delivery and monitoring. A summary of recent progress in nanotechnology as it relates specifically to nanoparticles and anticancer drug delivery will be reviewed. Nano nutraceuticals using combination of various natural products provide a great potential in cancer management. Additionally, various Nano-medicine approaches for the detection and treatment of various types of clots organ specific delivery, vascular targeting, improved PK/PD and vaccine will be briefly discussed. Highlighted Role of Nanobiotechnology and other enabling technologies in the followings: (1) Targeted drug delivery, (2) Improved PK and PD, (3) Early detection (Imaging), (4) Targeted delivery of chemotherapy for optimal efficacy and safety, (5) Nano synthesis and assembly of various platforms for targeted delivery and (6) Nanobiotechnology in shortening the time and risk of drug discovery and development.
- Nanomedicine and Drug Delivery | Drug Delivery and Therapeutics | Biosensors, Diagnostics and Imaging | Advanced Nanomaterials | DNA Nanotechnology
Chair
Hussein Ammar
Future University, Egypt
Co-Chair
Anthony William
University of Tokyo, Japan
Session Introduction
Anthony William
University of Tokyo, Japan
Title: Observing the molecular mechanical properties of DNA
Time : 12:10-12:30
Biography:
Anthony William Coleman has completed his BA in Chemistry and DPhil from the University of Sussex. He has authored 300 research articles, over 120 invited talks and 25 patents. He has numerous international projects underway in particular with the University of Tokyo elected FRSC in 2010.
Abstract:
The mechanical properties of DNA control both its containment in the nucleus and also the processes of transcription and construction of proteins. Hence, it is clear that knowledge of the properties that is a key to understanding how life is built. However, how to carry out such measurements without perturbing the inherent structure and properties of DNA is a major problem. Classical and even modern methods require modifying the chemical nature of DNA and hence its properties. The discovery of how microfluidics can be applied to silicon nano tweezer (SNT) measurement of the mechanical properties of non-modified DNA is a major step forward. Here, we will present how SNT technology can be used to study events changing the mechanical properties of DNA-(1) How physiological cations change selectively the mechanics of DNA as a function of the physiological localization, (2) The effects of DNA coordinating systems on DNA mechanics and how ion/bioactive couples can have amplified action and (3) The action of DNA coordinating nucleosomes on the structure of DNA.
Jinn P Chu
National Taiwan University of Science and Technology, Taiwan
Title: Thin film metallic glass: A promising coating for biomedical applications
Time : 12:30-12:50
Biography:
Jinn P Chu is a Professor of Materials Science and Engineering, National Taiwan University of Science and Technology (NTUST), Taiwan. He has completed his PhD in Materials Science from University of Illinois at Urbana-Champaign and has received the Excellence in Research Award in 2008 and became a Distinguished Professor at NTUST in 2012.
Abstract:
A new group of thin film metallic glasses (TFMGs) have been reported to show properties different from conventional crystalline metal films, though their bulk forms are already well-known for high strength and toughness, large elastic limits, excellent wear and corrosion resistance owing to their amorphous structure. In addition, the smooth surface, due to the grain boundary-free structure and low surface free energy of TFMGs can be achieved and lead to the relatively high hydrophobicity and the low coefficient of friction. In our studies, TFMG coatings are deposited using RF magnetron sputtering for various biomedical applications, including the property enhancements of dermatome blades and syringe needles as well as the antibacterial property. The TFMG-coated dermatome blades show great enhancements in sharpness and durability, compared with those of the bare one. For the syringe needle, the insertion and retraction forces were measured when needles were inserted into phantom materials, including polyurethane (PU) rubber block and pork muscle with a constant needle speed. TFMG-coated needle showed a significant reduction in both forces of ~66% and ~72%, respectively, which were significantly lower than those of bare needle during testing against the PU rubber. Furthermore, the bacterial adhesion of Escherichia coli and Staphylococcus aureus to both Zr- and Cu-based TFMGs is hindered to different extents. Good performances of TFMG and the antibacterial property are thought to be caused by the relatively low surface free energy and low coefficient of friction. Thus, TFMG coating appears to be a promising candidate for biomedical applications.
Miriam Colombo
University of Milano-Bicocca, Italy
Title: Oral nanocarrier for insulin colon delivery
Time : 13:50-14:10
Biography:
Miriam Colombo obtained her PhD in Biology in 2012 at the university of Milano-Bicocca. From September 2013 she is Assistant Professor in Clinical Biochemistry at the Dep. Biotechnology and Bioscience of University of Milano-Bicocca, Italy.She is author of 44 peer-reviewed scientific publications.
Abstract:
The current treatment of diabetes disease relies on insulin subcutaneous injection . Because of parenteral administration drawbacks, alternative administration routes have been investigated . Among all, the oral administration may lead to a better glucose regulation exploiting the liver first-pass metabolism of insulin, thus preventing the risks of fluctuating glycaemia. However, the oral bioavailability of peptides is very low and several efforts have been attempted to promote insulin bowel absorption. Despite all, the oral delivery of insulin remains an unmet need .The aim of work was to prepare, characterize and evaluate both in vitro and in vivo a novel nanoformulated multiple-unit colon delivery system, i.e. coated pellets, as a possible oral nanocarrier for insulin. Insulin-loaded polymeric nanoparticles (NPs) were synthesized according to previously published protocols with some improvements . The driving force of NPs formation was the opposite charges of polyethyleneimine and dextran sulphate resulting in the insulin entrapment into the polymeric matrix. NPs were incorporated into cores that were subsequently coated with three overlapping layers, aiming to release insulin into the large intestine: this gastrointestinal site is indeed characterized by a relatively low proteolytic activity. The system was evaluated in vitro for its physico-technological characteristics, NPs dispersion, disintegration and release performance, showing delayed release behavior. Finally, the coated nanoformulation effect was tested in diabetic rats: a significant hypoglycaemic activity, due to the synergistic effect of NPs and colon delivery, was observed. In this study, a new approach for the oral administration of insulin is proposed. The synergistic effect due to the nanoformulation of insulin and the encapsulation in a triple-layer pellet system for colon-release delivery results in a significant and long-lasting hypoglycemic effect. The impact of our multitasking macromolecule delivery system for oral insulin in controlling diabetes is clinically appealing, since it represents an oral route for insulin administration, with a prolonged hypoglycemic activity and a more physiological insulin metabolism.
Hoonsung Cho
Chonnam National University, South Korea
Title: Protamine conjugated fluorochromes: A new photosensitizer for photodynamic tumor therapy
Time : 14:10-14:30
Biography:
Hoonsung Cho is an Assistant Professor at Chonnam National University. He has earned his PhD degree from University of Cincinnati in 2010. He has joined Center for Advanced Medical Imaging Sciences at Massachusetts General Hospital in Boston, Massachusetts and extended his research into the field of multifunctional nanocarrier systems for imaging, targeting and therapy. His current research interests include imaging cell death with multimodal vital fluorochromes and detecting extracellular DNA and RNA using fluorochrome-functionalized nanoparticles as probes for detection and manipulation of these nucleic acids.
Abstract:
The Photodynamic therapy (PDT) is a promising alternative therapy that could be used adjunct to chemotherapy and surgery for curing cancer causing tissue destruction by visible light in the presence of a photosensitizer (PS) and oxygen. The high arginine peptides like the cell-penetrating peptide have membrane translocating and nuclear localizing activities that have led to their use in a wide range of drug delivery applications. Protamine is a high arginine peptide with membrane translocating and nuclear localizing properties. The reaction of an NHS-ester of methylene Blue (MB) and clinical protamine (Pro), to yield MB-Pro, was described in this context and demonstration of phototoxicity which clinical protamine improved PDT effect was performed. The reaction between clinical protamine (Pro) an NHS ester of MB is a solution phase reaction with the complete modification of the protamine peptides which feature a single reactive amine at the N-terminal proline and single carboxyl group at the C-terminal arginine. The aim of this study was to find a new type of photosensitizer (PS) for PDT on in vitro and in vivo experiments and to assess the anti-tumor effect of PDT using the protamine conjugated-PS on the cancer cell line. Photodynamic cell death studies show that the MB-Pro produced has more efficient photodynamic activities than MB alone, causing rapid light induced cell death. The attachment of MB to clinical Pro, yielding MB-Pro, confers the membrane internalizing activity of its high arginine content on methylene blue and can induce a rapid photodynamic cell death, presumably due to cell membrane rupture induced by light. The PDT using MB-Pro for HT-29 cells was very effective and those findings suggest that MB-Pro is one of candidate for photosensitizer in solid tumors.
Jessica Armida Bertolini
University of Milano-Bicocca, Italy
Title: Study and quantification of the endosomal escape mechanism for the delivery of nanoparticles as therapeutic agents
Time : 14:30-14:50
Biography:
Dr. Jessica A. Bertolini is a PhD in the Prof. Davide Prosperi’s NanoBioLab at the University of Milano-Bicocca. Her researcher activity is focused on biomedical applications of Nanotechnology, specifically on the use of cellular and molecular approaches to optimize and test nanoparticles, developed to be carrier of therapeutic agents, in cell cultures. Her current scientific interests concern the use of molecular biology techniques to prepare and modify DNA plasmids associated to nanoparticles, and cell biology techniques to test nanoparticles in cell cultures.
Abstract:
The improvements in nanomedicine are strictly dependent on the development of methods to deliver therapeutic agents specifically and efficiently to the target cells with minimal toxicity. One of the main mechanisms by which the nanoparticles are able to enter into mammalian cells takes advantage of an endocytic pathway of internalization. Nowadays, one of the principal problems that occur to the use of nanoparticles in nanomedicine is the degradation of the nanoparticles-associated therapeutic agents into cellular lysosomes, due to the difficulty for them to escape the endosomal pathway. Thus, the study of the endosomal escape mechanism becomes crucial to the development of efficient drug delivery nanosystems for therapeutic treatments .We developed a new approach to measure and quantify the endosomal escape mechanism of nanoparticles, using poly(isobutylene-alt-maleic anhydride)-graft-dodecyl amine (PMA) polymer normally used in our laboratory for colloidal nanoparticle coating. This synthetic polymer proved to be able to trigger the nanoparticle endosomal escape in previous investigations. A biarsenical fluorescent label fluorophore, called CrAsH, is linked to the PMA nanoparticles. The CrAsH fluorophore is non-fluorescent as such but, upon binding with proteins containing a tetra-cysteine motif Cys-Cys-Pro-Gly-Cys-Cys, becomes fluorescent (2;3;4). Cell cultures are previously transfected with a plasmid that encodes for a Blue Fluorescent Protein (5) linked to the tetra-cysteine motif in C-terminal region and later treated with PMA+CrAsH nanoparticles. The double fluorescence detection provides the quantification of the nanoparticles fraction, linked to the CrAsH fluorophore, able to reach the cytosol and recognize the tetra-cysteine target motif. Hence, this gives us a real measurement and quantification of the nanoparticle ratio able to really trigger the endosomal escape providing, thus, an estimation of the amount of therapeutic agents, potentially linked to the nanoparticles, that are actually able to reach the cellular cytoplasm and be available for medical treatment.
Yuqi Yang
Central China Normal University, China
Title: Labeling cells with fluorinated silicon nanoparticles for targeted 19F-MRI and Fluorescence Imaging
Time : 14:50-15:10
Biography:
Dr. Yuqi Yang received her PhD in 2015 from Central China Normal University, and then joined Wuhan Institute of Physics and Mathematics as an assistant proferssor. Dr. Yang’s study focuses on multi-modality contrast agents, especially specializes in nanomaterial-based agents for molecular imaging of tagrted cancer cells.
Abstract:
As a noninvasive molecular imaging modality, optical imaging provides high sensitivity and specificity but poor tissue penetration depth. On the contrary, MRI has high spatial resolution in deep tissue, but it suffers the drawbacks of low sensitivity. The combination of MRI and optical imaging, which takes advantages of both modalities, has received widespread attention in biological and medical application. Compared to conventional 1H-MRI, 19F-MRI displays an intense sensitivity (0.83 relative to 1H) and negligible background signal. Herein, we report a one-pot microwave synthesis of a functionalized 19F CA, fluorinated silicon nanoparticles (19F-SiNP), for targeted detection of A549 lung cancer cells. Moreover, based on the quantum effects of the nano-sized nanoparticles, the 19FSiNP can also act as a label free dye for ultracontrast fluorescent imaging. In vitro and in vivo results shows that the peptide-conjugated 19FSiNP can specifically detect A549 cells for dual 19F-MRI and fluorescence imaging. Such functionalized 19FSiNP can also be labeled to other cancer cells by replacing the targeting group, providing a handy and reliable way for targeted dual-model imaging.
Elham Ahmadi
Tabriz University of Medical Sciences, Iran
Title: PLGA-PAA copolymers: Their size and structure influenced drug delivery applications
Time : 15:50-16:10
Biography:
Elham Ahmadi is currently pursuing her Masters in Medical Biotechnology at Tabriz University of Medical Sciences and Bachelor’s degree in Cellular and Molecular Biology from Azarbijan Shahid Madani University, Tabriz. She is currently working on a project of nanotechnology based drug delivery for anti-cancer targeting and treatment.
Abstract:
Statement of the Problem: The need for high cellular drug uptake and reduce the adverse effects of chemotherapeutic drugs obligate us to design and prepare a suitable nano-carrier. Poly (lactide-co-glycolic acid) PLGA is one of the most well used polymer for the development of biocompatible nanoparticles.Purpose: The purpose of the study is to prepare the PLGA-PAA (Poly-lactide-co-glycolide)- (poly acrylic acid) co-polymer which is the first new developed biocompatible nano-carrier until now. We co-encapsulated hydrophilic doxorubicin and hydrophilic hydroxytyrosol in PLGA-PAA biocompatible nano-capsules.Methodology & Theoretical Orientation: We synthesized the poly (acrylic acid) (PAA) polymer by radical polymerization method in the presence of dry tetrahydrofuran as solvent of the reaction. Then the PLGA-PAA copolymer was synthesized by ring opening polymerization method in the presence of stannous Octanoate (snoct2) as catalyst of the reaction. An oil-in-water emulsion process was utilized for the encapsulation of hydrophilic doxorubicin and hydroxytyrosol.Findings: FTIR confirmed the PAA and PLGA-PAA copolymer formation is correct. HNMR, CNMR also approved it. The size of PLGA-PAA nanoparticles is measured 24 nm by DLS technique and a spherical particle with an average diameter of 16 nm is determined by SEM technique. The amount of drug loading and unloading is computed.Conclusion & Significance: PLGA-PAA co-polymer was found to be a promising co-polymer for the preparation of nanoparticles with small size distribution and relatively high drug loading. Formulation of functionalized PLGA-PAA nanoparticles leads to enhance the high drug loading efficiency of hydrophilic drugs.
Fatemeh sultani
Mashhad University of Medical Sciences, Iran
Title: In vitro evaluation of peptide-cholesterol hybrid as gene delivery nano-carrier
Time : 15:50-16:10
Biography:
Fatemeh Soltani has completed her PhD in Pharmaceutical Biotechnology from Mashhad University of Medical Sciences, Iran. She has worked on the synthesis of lipid-peptide core nanoparticles by using solid phase peptide synthesis (SPPS) methods. Currently, she is an Assistant Professor in Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Iran. Her research focuses on discovering efficient peptide, polymer or lipid-based drug/gene delivery vectors which are produced using either biological or synthetic methods.
Abstract:
Gene therapy has the potential to compensate the abnormal genes and treat both genetic and acquired disorders. For a successful gene therapy, a gene of interest must enter the cells successfully. To achieve this, an efficient and safe carrier is needed. Viral vectors are naturally based carriers and most widely used systems. Although they are efficient in gene transferring but they suffer from immunogenicity and toxicity. On the other hand, the non-viral counterparts such as lipids, proteins, polymers and peptides are safe enough to be considered as gene carriers for clinical application. However, their efficiency should be improved. Cationic peptides in particular to those derived from nature are important because they are biodegradable and biocompatible. They can be designed in order to develop multifunctional carriers having various functional motifs to improve gene delivery efficiency. Nuclear proteins such as protamine and histone are able to condense DNA and have been adopted in several gene delivery systems. However, the major concern related to these vectors is the risk of immunogenicity. To solve this drawback, some small peptides preserving the gene delivery properties of the whole protein have been chosen. In this study, we designed a cationic vector composed of a small cationic peptide derived from protamine as condensing agent and histidine tag for escaping from endosome. In order to form a micelle like particle, a cholesterol molecule was introduced to the N- terminal of the vector. The synthesized vector was evaluated in terms of structure, gene delivery efficiency and toxicity by using various standard methods. Based on the results the vector could form nano-micelle, condense pGFP and deliver it to the nucleus successfully. In addition, it showed negligible toxicity in comparison to PEI-25 kDa. Overall, further in vivo investigations are needed to shed light on the usage of these carriers in clinic.
Ramin Banan Sadeghian
Tohoku University, Japan
Title: Nano porous gold in 2D and 3D form, applications in ultrasensitive electrochemical superoxide bio-sensing
Time : 16:10-16:30
Biography:
Ramin Banan Sadeghian is an Assistant Research Professor in WPI-AIMR, Tohoku University. His expertise background and training are in microelectronics, VLSI processes, micro- and nano-fabrication, gas sensors, biosensors, semiconductor electron devices, thermo-electrics, instrumentation and industrial automation.
Abstract:
Superoxide anions as a member of reactive oxygen species (ROS) are involved in various physiological and pathological states. For instance, the rate of superoxide generation from skeletal muscle tissue is known to increase with contractile activity, fatigue and aging. It is therefore, very important to selectively detect and accurately quantify the release rates of super-oxides within both physiological and pathological levels. I will report on fabrication and characterization of enzyme-functionalized electrochemical superoxide biosensors built on a thick film of nanoporous gold and a three-dimensional macro-porous mesh of nanoporous gold. The devices were first tested and calibrated offline and then employed to detect superoxide release rates from C2C12 myoblast cells and myotubes upon stimulation with an endogenous superoxide producing drug. Two to three orders of magnitude higher sensitivities were achieved as compared to those of earlier reported devices.
Shizhen Chen
Chinese Academy of Sciences, China
Title: pH-Responsive theranostic nanocomposites as synergistically enhancing positive and negative magnetic resonance imaging contrast agents
Time : 16:30-16:50
Biography:
Dr. Shizhen Chen received her PhD in 2011 from Central China Normal University, and then began her post-doctoral research at Wuhan Institute of Physics and Mathematics. In 2013, she became an associate professor. Dr. Chen’s work focuses on magnetic resonance imaging (MRI) contrast agents, especially concentrated on the nanomaterial-based MRI contrast agents for lung cancer imaging.
Abstract:
The rational design of theranostic nanocomposite exhibiting synergistic turn-on of therapeutic potency and enhanced diagnostic imaging in response to tumor milieu is critical for efficient personalized cancer therapy.We here in fabricate a theranostic nanocomposites Mn-porphyrin & Fe3O4@SiO2@PAA-cRGD, which could synergistically enhancing positive and negative magnetic resonance imaging signals for both accurate tumor imaging and pH-responsive drug release. Fluorescent imaging also showed that the nanocomposite specifically accumulated in lung cancer cells by a receptor-mediated process, and were nontoxic to normal cells. The r2/r1 ratio varied is 20.6 in neutral pH 7.4 , r2/r1 ratio 7.7 in acidic pH 5.0, which suggesting the NCs could act as an ideal T1/T2 dual-mode contrast agents at acidic environments of tumor areas. For in vivo MRI, T1 and T2 relaxation was significantly accelerated to 55% and 37%, respectively, in the tumor after i.v. injection of nanocomposites. The results demonstrate great potential of such nanocomposites for real-time imaging with greatly enhanced diagnostic accuracy during targeted therapy.
- Drug Delivery and Therapeutics | Biosensors, Diagnostics and Imaging | Advanced Nanomaterials | DNA Nanotechnology
Chair
Stoyan Sarg Sargoytchev
World Institute for Scientific Exploration, USA
Co-Chair
Anthony William
University of Tokyo, Japan
Session Introduction
Davide Prosperi,
University of Milano-Bicocca, Italy
Title: Dependence of in vivo tumor homing, localization and therapeutic effect of colloidal nanoparticles on the number of attached antibodies
Time : 12:00-12:20
Biography:
Dr. Prosperi is an Associate Professor in Biochemistry at the University of Milano-Bicocca. Since 2008, he is the head of the NanoBioLab, http://www.nanobiolab.btbs.unimib.it. His research activity has been focused on biomedical and biophysical applications of Nanotechnology. His current scientific interests concern: synthesis, functionalization and characterization of nanoparticles for biomedical applications; biophysical studies on colloidal systems; studies of interaction of nanostructures with biological systems. The group of DP has developed innovative methods for surface bioengineering of colloidal and biomimetic nanoparticles and for the characterization of resulting hybrid nanoparticles. He is an author of over 90 scientific publications.
Abstract:
Colloidal nanoparticles (NPs) are a versatile tool to integrate nanotechnology and biology, provided that they are complemented with a proper surface functionalization. To this aim, several strategies have been proposed in the attempt to optimize the surface modification of NPs with organic and biological targeting ligands to improve the NP affinity towards biological receptors (1). Several studies have been developed to achieve a control on linkage stability (2), as well as on ligand orientation and density (3). However, a general strategy to introduce a discrete precisely controlled number of targeting biomolecules to each NP is still largely missing. In particular, active targeting of NPs to tumors can be achieved by conjugation with specific antibodies. In the present work (4), specific active targeting of HER2 receptor is demonstrated in vitro and in vivo with a subcutaneous MCF-7 breast cancer mouse model with trastuzumab-functionalized gold nanoparticles (Au NPs), utilizing IgG antibody-modified Au NPs as nonspecific control. The number of attached antibodies per NP was precisely controlled in a way that each nanoparticle was conjugated with either exactly one (5NP-1Tz), or exactly two antibodies (5NP-2Tz). In vitro we found a moderate increase in targeting efficiency of nanoparticles with two instead of just one antibody attached per nanoparticle. However, despite an intuitive belief that also in vivo targeting efficiency should rise upon increasing the amount of antibodies per nanoparticle, the in vivo data demonstrate that best effect is obtained for nanoparticles with only exactly one antibody per nanoparticle. There is indication that this is based on as size-related effect. These results highlight the importance of precisely controlling the ligand density on the nanoparticle surface for optimizing active targeting, and that less antibodies can exhibit more effect.
Fawad ur Rehman
Southeast University, China
Title: Cancer cell is an excellent scaffold for nanomaterials biosynthesis and theranostics of metastasis
Time : 12:20-12:40
Biography:
Fawad Ur Rehman is currently a Postdoctoral Fellow in Professor Xuemei Wang’s Lab at State key laboratory of Bioelectronics, Southeast University, Nanjing China. He has completed his PhD degree from the same institute, Master’s from The University of Agriculture, Peshawar and Doctor of Veterinary Medicine (DVM) degree from the University of Veterinary and Animal Sciences, Lahore Pakistan. His current research interests include nanoscale materials in situ biosynthesis and their biomedical application in synergy to pluripotent stem cells for various diseases theranostics, especially cancer.
Abstract:
Statement of the Problem: Nanoscale materials and biomedical applications are exponentially increasing each passing day, especially in cancer theranostics and drug delivery system. The nanomaterials synthesis procedure is complex and involves various toxic chemicals. Therefore, the biomedical scientific community has serious health hazard concerns. To overcome the associated complications, a green synthetic approach has been introduced to biosynthesize via plants, bacteria, fungi and algae and most recently redox imbalance mammalian cells i.e. tumor and neurodegenerative maladies.Methodology & Theoretical Orientation: We have simply introduced the pre-ionic solution of metals viz. HAuCL4 (Gold), FeCl2 (Paramagnetic Iron), Na2SeO3 etc. to the cancer cell lines (HepG2, HeLa, U87, SGC-7901 etc.) to biosynthesize the nanoprobes for cancer multimode bioimaging via fluorescence, CT and MRI, both in vitro and in vivo.Findings: 24 hours post injecting the relevant pre-ionic solutions (40µl/ml), the cells started fluorescence under confocal microscope. After physical lysis, the relevant nanoclusters were isolated from the cells. The nanoclusters were analyzed via TEM, XPS, Cell Mapping, FTIR and the size was ranged <5 nm. All the cancer cells in vitro and tumor xenograft models in vivo exhibited fluorescence and performed as contrast agents for CT and MRI by successfully marking tumor. The in situ biosynthesized nanoclusters were highly biocompatible and had no adverse effects to vital organs.Conclusion: The in situ biosynthesized nanoclusters by using cancer cells and tumor microenvironment were highly biocompatible and were excellent probes for multimode bio-imaging.
Keka Sarkar
Universiy of Kalyani, India
Title: Curcumin nano-formulation as potential nano-medicinal approach for effective cancer therapy
Time : 12:40-13:00
Biography:
Keka Sarkar is currently the Associate Professor in the Department of Microbiology at the University of Kalyani, India.
Abstract:
Curcumin, a low molecular weight natural polyphenol found in the plant Curcuma longa (turmeric), is well known for showing anti-oxidant and anti-inflammatory activities and might be potential candidate for the prevention and/or treatment of cancer and other chronic diseases. Though, being highly pleiotropic molecules with an excellent safety profile targeting multiple diseases with strong evidence on the molecular level, curcumin could not achieve its optimum therapeutics outcome in past clinical trials, largely due to its poor bioavailability. Hence, encouraging progress in the field of nano-scale drug delivery system has been employed to improve the delivery approach for curcumin. Biodegradable polymer based nanoparticles (NPs) were formulated with a view to improve its bioavailability. Curcumin loaded chitosan NPs (CSCur) were prepared by the polyanion-initiated gelation process. The biophysical parameters of the synthesized nanoparticles were determined by means of dynamic laser scattering (DLS), atomic force microscopy (AFM), fourier transform–infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). Further, evaluation of anticancer activity, effect of CSCur NPs on cell growth, cell viability (MTT) assay and apoptotic molecular mechanism studies was carried out with HeLa cell line. The cytotoxicity studies were revealed that the CurCS NPs offer specific toxicity on cancer cells. Our studies achieved successful formulation of CSCur nPs, thus indicating that NPs could be a potential vehicle for curcumin drug delivery and enabling its enhanced absorption and cellular uptake. The main activity of our laboratory deals with design and development of nanoparticles, nano-colloids, drugs and molecular carrier design, cellular imaging and molecular detection applied in the field of life science. Our group develops and characterizes different metallic and polymeric nanoparticles, surface modification of materials at nanometer scale. We have introduced the techniques utilizing nano-materials in the perspective of applied microbiology, molecular detection and personalized medicine, providing well suited therapies for better efficiency and limited side effects. Our research also focuses on understanding the responses of microbial communities to different stresses, with an emphasis on linking community structure to identify the key indicators through data assessment.
Preenan Pillay
University of KwaZulu-Natal, South Africa
Title: Placental-derived exosomes: Future biomarkers of pree
Time : 14:00-14:20
Biography:
Preenan Pillay has his experience in technology transfer, production of recombinant proteins upstream/downstream bioprocess optimization, teaching and learning and academic program management. His recent area of interest in nano-medicine is the investigation of the potential application of exosomes as biomarkers of preeclampsia.
Abstract:
Statement of the Problem: Hypertensive disorder in pregnancy (HDP) is one of the leading causes of maternal and perinatal morbidity, affecting up to 10% of pregnancies globally. Pre-eclampsia (PE) is the most predominant HDP result in 50,000-76,000 maternal deaths per a year worldwide. Pre-eclampsia still remains an enigmatic scientific research question due to its unknown etiology, which is related to the multifactorial nature of the disorder. Angiogenic, antiangiogenic, cffDNA, cfDNA and proteins have been extensively studied as potential biomarkers of PE, however, with no definitive diagnosis/prognosis. More recently, exosomes have emerged as potential biomarkers of PE due to their potential immune-regulatory role in pregnancy. Exosomes are cellular derived organelles, containing molecular cargo such as- membrane bound proteins, cytosolic RNA and lipids, which serve as valuable tools in PE biomarker discovery. In this preliminary study, we have determined the concentration of total and placental-derived exosomes in maternal circulation.Methodology & Theoretical Orientation: This study forms the basis for future studies for the identification of placental-derived exosomal molecular markers of PE since the preliminary requirements of a biomarker is for it to be (1) objectively isolated is detected and quantified in biofluids and (2) shown to be significantly altered in PE in comparison to normal pregnancy. Plasma samples were obtained from pregnant women in the third trimester, for the isolation of exosomes by differential ultracentrifugation. Total exosomes were quantified using nanoparticle tracking analysis and immuno-reactive exosomal CD63 quantification. Placental-derived exosomes were quantified using placental alkaline phosphatase (PLAP) as a specific marker. The contribution of placental-derived exosomes to total exosomes in maternal plasma was determined by the ratio of PLAP+ exosomes to CD63+ exosomes.Findings: The outcomes of the study indicate that the number of exosomes present in maternal circulation is higher in early and late onset PE compared with normal pregnancy. However, placental-derived exosomes are significantly lower in late onset PE compared to early onset PE and normal. Moreover, the contribution of placental exosomes to total exosomes increases in early onset PE but decreases in late onset PE. Conclusion & Significance: These findings provide insight into the physiological levels of total and placental-derived exosomes in early onset and late onset PE, which can be used as a basis for future studies to fully elucidate the role of these molecules in PE. Additionally, the findings indicate that exosomes may serve as a promising biomarker of early onset and late onset PE and therefore warrants further investigation.
Wendy N Phoswa
University of KwaZulu-Natal, South Africa
Title: Effect of titanium dioxide nanoparticle aggregation on myoblast cytotoxicity and nitric oxide synthesis
Time : 14:20-14:40
Biography:
Wendy N Phoswa has her expertise passion in improving nanotechnology. Her research based on the titanium dioxide nanoparticles creates new pathways for improving titanium dioxide physiochemical properties for nanoparticles toxicological. She has experience in research, evaluation, teaching and administration in education institutions.
Abstract:
Statement of the Problem: The emerging interest of engineered titanium dioxide nanoparticles (TiO2 NPs) in medical, agricultural, industrial and manufacturing sectors has raised health questions worldwide. Therefore, the objective was to assess the effect of physiochemical properties of titanium dioxide nanoparticles (TiO2 NPs) on the cellular cytotoxicity, proliferation and physiological properties.Methodology & Theoretical Orientation: TiO2 NPs were suspended in varying concentrations of bovine serum albumin (BSA γ-globulin) and characterized using nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) for the determination of particle size, aggregation state and zeta potential. The effect of TiO2 physiochemical properties on cellular cytotoxicity and proliferation was assessed in vitro on mouse myoblast (C2C12) cells using the MTT assay and BrdU assay, respectively. Nitric oxide is a major signaling molecule was measured using colorimetric measurement to indirectly assess cellular activity.Findings: The cytotoxicity of mono-disperse TiO2 NPs suspended in BSA were significantly higher in comparison to the controls (p<0.001). A significant increase in the cytotoxicity of TiO2 NPs suspended in BSA at a concentration of 0.5, 0.8 and 1 mg/ml BSA in contrast to 0.3 and 1.5 mg/ml BSA was obtained (p<0.05). However, there was a more significant increase in cytotoxicity levels of TiO2 NPs suspended in 0.8 mg/ml BSA compared to TiO2 suspended in 0.3, 0.5, 1 and 1.5 mg/ml BSA concentrations (p<0.05). In addition, there was also a significant difference in DNA proliferation of the control and treated cells. A significant difference in DNA damage was observed in cells treated with TiO2 NPs compared to non-treated cells and cells treated cells treated with BSA concentrations (0.8 and 1.5 mg/ml). There also a significant difference in DNA damage in cells treated with TiO2 NPs in combination with BSA (0.8 and 1.5 mg/ml). There was more significant difference in DNA damage of cells treated with TiO2 NPs in combination with 0.8 mg/ml compared to TiO2 NPs in combination with 1.5 mg/ml. There was also reduced nitric oxide bioavailability in cells treated with TiO2 NPs.Conclusion & Significance: The use of BSA as a nanoparticle stabilizer helped to improve particle physiochemical properties for the determination of in vitro cytotoxicity. The findings indicate that particle size needs to be taken into consideration when assessing nanoparticle toxicity since BSA generates smaller TiO2 NPs aggregates which have a potential to inhibit cellular signaling which results in cytotoxicity.
Marta Perez Lloret
Università degli Studi di Catania (Italy).
Title: Polymeric film releasing nitric oxide under light stimulation, reported by fluorescence.
Time : 14:40-15:00
Biography:
Marta Pérez Lloret got her MSc at Universidad de Zaragoza (Spain) and actualy is a PhD candidate in the project Cyclon-Hit, from MSCA at Università degli Studi di Catania (Italy).
Abstract:
Global health organizations are concerned about the multi-drug resistance (MDR). This phenomenon is presumed to set off one of the most important health crisis in our history. Thanks to the misuse of antibiotics, together with the capacity of microorganisms to adapt them to survive in hostile conditions, “traditional antibiotics” are becoming obsolete. Here in born the need to create smart material acting as antibiotics. An interesting approach to defeat this issue is the production of cytotoxic species, such as NO, singlet oxygen and heat, which do not present MDR. Some advantages of light-triggered production of cytotoxic species are its good spatiotemporal release control, fast reaction rates and the absence of residues after the reaction. A hybrid compound was specifically design and produce in our group, containing a coumarin (fluorescent marker), linked to a NO-photodonor and posteriorly incorporated into poly (lactic- co-glycolic acid)-based (PLGA) film. It is expected to observe a fluorescence-quenching effect between the NO-photodonor and the fluorophore through Forster resonance energy transfer (FRET). After the NO release, no energy transfer occurs, leading to the revival of fluorescence of the coumarin. Thanks to the transparency of this biocompatible polymeric film, after the NO release, fluorescence emission will allow us to monitor indirectly its release by fluorescence imaging. The importance of monitoring NO photo-production resides in its dosage-dependent effect. A relation between irradiation time and death rate was proved during antibacterial tests.