Day 1 :
Keynote Forum
Edouard Alphandéry
Sorbonne Universités, France
Keynote: Development of non-pyrogenic magnetosome minerals coated with poly-L-lysine leading to full disappearance of intracranial U87-Luc tumors in 100% of treated mice using magnetic hyperthermia
Biography:
Edouard Alphandéry has completed his PhD from Oxford University and Postdoctoral studies from Trinity College and the University of Washington. He is an Assistant Professor at the UPMC, France. He has published more than 30 papers in reputed journals and submitted 10 patent families.
Abstract:
Magnetic hyperthermia was reported to increase the survival of patients with recurrent glioblastoma by seven months. This promising result may potentially be further improved by using iron oxide nanoparticles, called magnetosomes, which are synthesized by magnetotactic bacteria, extracted from these bacteria, purified to remove most endotoxins and organic material, and then coated with poly-L-lysine to yield a stable and non-pyrogenic nanoparticle suspension. Due to their ferrimagnetic behavior, high crystallinity and chain arrangement, these magnetosomes coated with polylysine (M-PLL) are characterized by a higher heating power than their chemically synthesized counterparts currently used in clinical trials. M-PLL PLL-enhanced antitumor efficacy was demonstrated by administering 500 to 700µg in iron of M-PLL in to intracranial U87-Luc tumors of 1.5mm3 and by exposing mice to 27 magnetic sessions of each lasting 30 minutes, during which an alternating magnetic field of 202kHz and 27mT was applied. Treatment conditions were adjusted to reach a typical hyperthermia temperature of 42°C during the first magnetic session. In 100% of treated mice, bioluminescence due to living glioblastoma cells fully disappeared 68 days following tumor cell implantation (D68). All these mice, which were all still alive at D350. Histological analysis of their brain tissues revealed an absence of tumor cells, suggesting that they mice were fully cured. In comparison, antitumor efficacy was less pronounced in mice treated by the administration of IONP followed by 23 magnetic sessions, leading to full tumor bioluminescence disappearance in only 20% of the treated mice.
- Nanomedicine and Biomedical Applications| Design of Nanodrugs| Nanomedicine and Nanotechnology| Synthesis of Nanoparticles for Drug Delivery| Novel Drug Delivery Systems
Location: Meeting place 2
Chair
Sergey Suchkov
Sechenov University, Russia
Session Introduction
Aiman Abu Ammar
Azrieli College of Engineering Jerusalem, Israel
Title: Controlled release of steroids utilizing drug-eluting endotracheal tube
Biography:
Aiman Abu Ammar is a Faculty Member in the Department of Pharmaceutical Engineering at Azrieli College of Engineering, Israel. He has completed his Pharmacy studies, MSc in Medicinal Chemistry, and PhD in Pharmaceutical Sciences at The Hebrew University of Jerusalem. He has joined Nanoengineering Group at Technion, as Senior Scientist. He is a licensed Pharmacist and has research experience in nano-drug delivery systems for the treatment of solid tumors and performs multi-disciplinary research with a focus on development of localized drug delivery systems using nanotechnology. He is a Co-inventor of 1 patent in this field.
Abstract:
Intubation-related morbidity is a common complication that usually involves the larynx and trachea, leading to local irritation, inflammation, and edema. Such complication is secondary to airway mucosal damage due to the use of an endo-tracheal tube (ETT), which produces local pressure and a pressure-like ulcer. The common clinical approach to manage airway mucosal damage is systemic administration of steroids hours to days prior to extubation, however, such treatment is inadequate, and some patients will need to undergo tracheostomy. Herein, steroid-eluting ETT for local treatment was developed for the purpose of improving drug efficiency and avoiding systemic steroid related side effects. Electrospinning technique was utilized to coat ETTs and produce a microscale layer of poly (lactic-co-glycolic acid) (PLGA) nanofibers loaded with Mometasone Furoate (MF). The novel delivery system was fully characterized, by means of drug loading, morphology, and mechanical stability of fiber mats. Moreover, in vitro release study demonstrated controlled release of MF over 14 days. The MF-coated ETTs exhibited superior therapeutic response compared to blank ETTs using an in vivo rat model, in terms of reduced laryngeal mucosal thickness and submucosal laryngeal edema. Taken together, steroid-loaded ETT is a novel approach allows for local drug delivery in a controlled manner, for improved treatment of intubation-related morbidity.
Sergey Suchkov
I M Sechenov First Moscow State Medical University, Russia
Title: Antibody-proteases as a novel biomarker and a unique target for translational applications to be applied for bioengineering and biopharma
Biography:
Sergey Suchkov has graduated from Astrakhan State Medical University and awarded with MD, then in 1985, completed his PhD at the I.M. Sechenov Moscow Medical Academy and in 2001, completed his Doctorship Degree at the Nat. Inst. of Immunology, Russia. From 1987 through 1989, he was a senior Researcher, Koltzov Inst. of Developmental Biology. From 1989 through 1995, he was a Head of the Lab of Clinical Immunology, Helmholtz Eye Research Institute in Moscow. From 1995 through 2004, a Chair of the Dept for Clinical Immunology, Moscow Clinical Research Institute. He has been trained at: NIH; Wills Eye Hospital, PA, USA; Univ. of Florida in Gainesville; UCSF, S-F, CA, USA; Johns Hopkins University, Baltimore, MD, USA. 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 the Chair, Dept. 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; EPMA (European Association for Predictive, Preventive and Personalized Medicine), Brussels, EU; ARVO (American Association for Research in Vision and Ophthalmology); ISER (International Society for Eye Research) and PMC (Personalized Medicine Coalition), Washington, USA.
Abstract:
Catalytic Abs (catAbs) is multivalent immunoglobulin’s (Igs) with a capacity to hydrolyze the antigenic (Ag) substrate. In this sense, proteolytic Abs (Ab-proteases) represents Abs to provide proteolytic effects. Abs against myelin basic protein/MBP with proteolytic activity exhibiting sequence-specific cleavage of MBP is 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.
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Recent Publications:
- Ponomarenko N A, Durova O M, Vorobiev I I, Aleksandrova E S, Telegin G B, Chamborant O G, Sidorik L L, Suchkov S V, Alekberova Z S, Gnuchev N V and Gabibov A G (2002) Catalytic antibodies in clinical and experimental pathology: human and mouse models. Journal of Immunological Methods. 269 (1-2): 197-211.
- Ponomarenko N A, Durova O M, Vorobiev I I, Belogurov A A, Telegin G B, Suchkov S V and A G Gabibov (2005) Catalytic activity of autoantibodies toward myelin basic protein correlates with the scores on the multiple sclerosis expanded disability status scale. Immunol. Lett. 103 (1): 45-50.
- Gabibov A G, Ponomarenko N A, Tretyak E B, Paltsev M A, Suchkov S V (2006) Catalytic autoantibodies in clinical autoimmunity and modern medicine. Autoimmunity Reviews. 5 (5): 324-330.
- Gabibov A A, Paltsev M A, Suchkov S V (2011) Antibody-associated proteolysis in surveillance of autoimmune demyelination: clinical and preclinical issues Future Neurology. 6 (3): 303-305.
- D Kostyushev, I Tsarev, D Gnatenko, M Paltsev, S Suchkov (2011) Myelin-associated serological targets as applicable to diagnostic tools to be used at the preclinical and transient stages of multiple sclerosis progression. Open J Immunology. 1 (3): 80-86.
Bita Rasoulian
Iran University of Medical Sciences, Iran
Title: The core of self-assembling peptide nanofibers will influence neurogenesis potential of its attached biological motif
Biography:
Bita Rasoulian has completed her graduation from Maziar University, Royan, Mazandaran in the field of Biomedical Engineering and Biomaterials. She is a Research Assistant of Nanomedicine under Supervision of Dr. Shima Tavakol at Cellular and Molecular Research Center, Iran University of Medical Science. However, she is interested in the investigation of nanomaterials and their influence and interaction with biological systems especially nervous and bone. Meanwhile, she has expertise in in-vitro and in-vivo studies, as well. Her major researches have been on spinal cord injuries and craniofacial injuries, modeling and treating them with various specified nanomedicines in which she has gained exclusive results.
Abstract:
To date, spinal cord injury (SCI) has remained an incurable disaster. The use of self-assembling peptide nanofiber containing bioactive motifs such as bone marrow homing peptide (-BMHP1) as an injectable scaffold in spinal cord regeneration has been suggested and investigated earlier. Although, in all the investigation, the effect of biological motifs have been investigated but the influence of self-assembling core of peptide nanofibers in tissue engineering has been neglected. In the present investigation for the first time, the influence of two major core of self-assembling peptide nanofibers attached to the famous neurogenic biological motif of BMHP1 was assessed. BE2M17 one of the reference cell line (human neuroblastoma cell line) in neurological investigation was choose and cells were treated with the peptide nanofibers and cell behavior investigated. Then cells were differentiated for four days and neural genes were assessed by real time PCR. To investigate the spinal cord recovery potential of nanofibers, they were implanted into a chronic model of SCI in rat. Results showed that the core of KSL-B induced higher cell viability and LDH release while the core of RADA-B exhibits higher acidic environment and induced more ROS, NO production and higher amount of PI positive cells (Dead cells) with higher percentage of Sub-G1 in cell cycle characterized by flowcytometery. However, these results were in good agreement with BAX/BCL2 ratio indicated higher BAX/BCL2 ratio for cells treated by RADA-B. Interestingly, the RADA-B induced higher gene expression of nNOS in agreement with NO production. Results showed that although RADA-B induced higher gene expression of Integrin 5 as a cell membrane signaling receptor but KSL-B over-expressed higher gene of focal adhesion kinase 2 as a downstream of integrin and resulted in higher gene expression of Nestin, MAP2, TH, GFAP and GDNF while the over-expression of NF and GABA was higher in RADA-B. Interestingly, RADA-B induced over-expression of GABA while, KSL induced over-expression of TH. The BBB score of spinal cord injury model in rat disclosed that KSL-B induced higher motor recovery in rats. In conclusion, it might be said that based on the targeted tissue the core of self-assembling peptide nanofiber must be choose. In a bone with acidic friendly environment the RADA core would be better (data not shown) while in the neural tissue, KSL with less inducible acidic environment would be preferred.
Biography:
Edouard Alphandéry has completed his PhD from Oxford University and Postdoctoral studies from Trinity College and the University of Washington. He is an Assistant Professor at the UPMC, France. He has published more than 30 papers in reputed journals and submitted 10 patent families.
Abstract:
Biologics magnetics nanoparticles, magnetosomes, attract attention because of their magnetic characteristics and potential applications. The aim of present study was to develop and characterize a novel magnetosomes extracted from magnetotactic bacteria, purified to produce apyrogen magnetosome minerals, and then coated with chitosan, neridronate, or polyethyleneimine, to yield stable magnetosomes designated as M-Chi, M-Neri, and M-PEI, respectively. The biocompatibility of nanoparticles was evaluated with mouse fibroblast cells (3T3), Mouse glioblastoma cells (GL-261) and Rat glioblastoma cells (RG-2). Also, we tested these nanoparticles for magnetic hyperthermia treatment of tumor in vitro with GL-261 exposed an alternating magnetic field, heating properties, efficiency and internalization was then evaluated. Nanoparticles coated with chitosan, polyethyleneimine and neridronate are apyrogen, biocompatible and stable in aqueous suspension. The presence of a thin coating in M-Chi and M-PEI favors an arrangement in chains of the magnetosomes, similar to that observed in magnetosomes directly extracted from magnetotactic bacteria, while the thick matrix embedding M-Neri leads to structures with an average of 3.5µm2 per magnetosome mineral. In the presence of GL-261 cells and upon application of an alternating magnetic field, M-PEI and M-Chi lead to the highest specific absorption rates of 120-125W/gFe. Furthermore, while M-Chi lead to rather low rates of cellular internalization, M-PEI strongly associate to cells, a property modulated by application of an alternating magnetic field. Coating of purified magnetosome minerals can therefore be chosen to control the interactions of nanoparticles with cells, organization of the minerals, as well as heating properties and cytotoxicity, which are important parameters to be considered in the design of a magnetic hyperthermia treatment of tumor.
Zumra Peksaglam
University of Southern California, USA
Title: Light-sensitive nanoparticles for Bcl-2 siRNA and paclitaxel co-delivery
Biography:
Zumra Peksaglam has completed her BS in Chemical Engineering from Gazi University (Ankara, Turkey) in 2012, and MS in Chemical Engineering from University of Southern California (USC) in 2016. Currently, she is studying photo-triggered surfactant systems for control of protein unfolding and gene delivery at Dr. Charles Ted Lee’s laboratory as a 3rd year PhD student at USC. She is also 2nd year student of Health, Technology and Engineering graduate certificate program which is an interdisciplinary program between Viterbi Engineering and Keck School of Medicine.
Abstract:
Light-sensitive nanoparticles for siRNA and Paclitaxel co-delivery: They are catanionic vesicles that are formed spontaneously upon the interaction of an azobenzene-based cationic surfactant and a conventional anionic surfactant. As a result of the photo-responsive property of azobenzene moieties, the light-sensitive microstructure can be switched with light illumination from vesicles to micelles, lamellar structures, or free surfactant monomers. The usage of nanoparticles for chemotherapeutic drugs has a potential to increase cancer treatment efficiency. Additionally, a prospective therapeutic genetic material, siRNA, can be used to deactivate targeted mRNAs that cause inhibition of disease-associated protein production. Thus, the unique photo-assisted transition of vesicles to free monomers of light-sensitive nanoparticles were used to encapsulate both siRNA and a chemotherapeutic drug, Paclitaxel, to cancer cells and, then control the release of them by UV light exposure. In this work, the effect of hydrophobic tail of cationic surfactants on particle size, charge and surface characteristics are measured by small-angle neutron scattering (SANS), dynamic light scattering (DLS), zeta potential meter and cryo-transmission electron microscopy (cryo-TEM) to create an ideal delivery vector. The encapsulation efficiency and cellular uptake capability of Bcl-2 siRNA and Paclitaxel co-delivery through MDA-MB-231 human breast cancer cells are explored as 8:1 ratio of vesicle:PTX and 10:1 (w:w) N:P ratio (vesicle/siRNA) with 45% of cellular uptake. Therefore, azobenzene-based catanionic vesicles are used as a co-delivery nanovehicle to develop siRNA-based therapeutics with a hydrophobic anticancer drug. It is expected to improve tumor therapeutic efficacy by the usage of the unique photo-assisted delivery agent.
Bita Rasoulian
Iran University of Medical Sciences, Iran
Title: Size of NPs in a nano drug formulation along with co-surfactant concentration will define transduction signals and cell biocompatibility
Biography:
Bita Rasoulian has completed her graduation from Maziar University, Royan, Mazandaran in the field of Biomedical Engineering and Biomaterials. She is a Research Assistant of Nanomedicine under Supervision of Dr. Shima Tavakol at Cellular and Molecular Research Center, Iran University of Medical Science. However, she is interested in the investigation of nanomaterials and their influence and interaction with biological systems especially nervous and bone. Meanwhile, she has expertise in in-vitro and in-vivo studies, as well. Her major researches have been on spinal cord injuries and craniofacial injuries, modeling and treating them with various specified nanomedicines in which she has gained exclusive results.
Abstract:
Todays, nano-pharmaceutics as a major branch of nanomedicine has developed and there are some nanoformulations in market with less side effect and high efficacy and bioavailability in patients. Although, the basic investigation in this field has critical importance to design of safer nanoformulation but there are no reports that investigate in parallel the effect of ethanol concentrations as a major co-surfactant in nanoemulsions and some other type of nanoformulations along with the particle size. So, for the first time, NPs with equal and different particle size at same and different concentrations of ethanol were prepared and their influence on cell behavior and inflammatory and apoptosis genes were investigated. NPs with no ethanol were nominated 3.10 and at the ethanol concentrations of 3 and 5% were nominated 3.10.3 and 3.10.5 and if the temperature was applied they were nominated 3.10T, 3.10.3T and 3.10.5T. The particle size of 3.10 and 3.10.3 were same and had a mid diameter of 56.8nm, however temperature applying resulted in larger particle size in both group, 78.9 and 77.7nm, respectively. Increase of ethanol concentration from 3 to 5 % decreased particle size in non-temperature and temperature formulations to 47.9 and 70.7nm, respectively. Thermodynamic stability showed no sign of biphasic and physical appearance in the formulations and TLC disclosed that all the nano-formulations had equal Rf of 0.14. Based on the mentioned results, it might be said that temperature, surfactant, co-surfactant and the preparation method not damage to the curcumin as a drug substitute. In conclusion, it might be said that the particle with average diameter of 70-78nm were more up-taken by cells than smaller ones and induce more integrin gene expression and larger ones exhibit less damaging effects on cell membrane and induces less intracellular ROS production and afterwards iNOS gene expression and inflammatory gene of NF-KB. However, smaller nanoformulation around 49-56nm exhibited higher cell viability by the MTT assay, BCL2 gene expression and less NO production. Based on our findings, it seems that cell viability FAK2 gene expression have more direct effect than integrin gene over-expression and cell up take on cell migration and the 3.10, 3.10T and 3.10.5T induce higher cell migration than others, respectively that they were in good agreement with the FAK2 gene over-expression.