Miriam Royo, Scientific Coordinator of Unit 3 of NANBIOSIS explains in this video the expertise of the unit in the preparation of difficult peptides (Cyclid and polycyclic peptides, stapled peptides and dificult peptides, depsipetides, natural products and libraries, peptidomimetic libraries, peptides as antigens or adjuvants, tarjeted drug conjugates, etc… as well as therapeutic agen-PEG-targeting unit conjugates
NANBIOSIS Unit 6 Biomaterial Processing and Nanostructuring and Unit 3 Synthesis of Peptides collaborate in a research whose results are published by The Journal of Physical Chemistry B
Stimuli-responsive self-assembled monolayers (SAMs) are used to confer switchable physical, chemical, or biological properties to surfaces through the application of external stimuli. To obtain spatially and temporally tunable surfaces, we present microcontact printed SAMs of a hydroquinone molecule that are used as a dynamic interface to immobilize different functional molecules either via Diels–Alder or Michael thiol addition reactions upon the application of a low potential. In spite of the use of such reactions and the potential applicability of the resulting surfaces in different fields ranging from sensing to biomedicine through data storage or cleanup, a direct comparison of the two functionalization strategies on a surface has not yet been performed. Although the Michael thiol addition requires molecules that are commercial or easy to synthesize in comparison with the cyclopentadiene derivatives needed for the Diels–Alder reaction, the latter reaction produces more homogeneous coverages under similar experimental conditions.
Yesterday took place in Barcelona, at Barcelona School of Management, Universitat Pompeu Fabra, a meeting of resarch groups and units of NANBIOSIS and CIBER-BBN and companies in the third B2B Forum organized by NANBIOSIS, in this case together with NANOMED SPAIN.
Thirteen companies and twelve groups from CIBER-BBN and CCMIJU (ten of them coordinating NANBIOSIS units) got together to explain, through short presentations of ten minutes, those lines of their work aimed at finding synergies and potential collaborations in the area of Nanomedicine apllications in drug delivery and targeting. There was also a talk by a representative of CDTI (Spanish National Center for Industrial and Technological Development) to explain the financing opportunities for the companies as well as a presentation by the NANBIOSIS Coordinator, Jesús Izco, to show the new Cutting Edge Biomedical Solutions offered by the ICTS-NANBIOSIS.
After lunch, the groups and companies had the opportunity to discuss in more detail, during bilateral interviews coordinated by NANBIOSIS a, those aspects that had attracted their attention, as well as, in some cases, to draw potential collaborations. The event was successfully developed with 45 attendees and more than 50 individual B2B mettings.
In the framework of the FEDER Program in ICTS 2014-2020, several projects related to the ICTS NANBIOSIS have been selected by the MINECO for co-financing with FEDER funds of the European Regional Development Funds program.
An agreement has been signed between MINECO and CIBER (partner of NANBIOSIS for the co-financing of the Project: “Purchase, installation and set-up of production and characterization equipment to complement the Units: U3-Synthesis of Peptides Unit, U18-Nanotoxicology and U20- In Vivo Experimental Platform”. The total budget of the project amounts to € 307,566.16, with 50% financing with FEDER Funds.
Also CSIC (The State Agency Superior Council of Scientific Investigations), institution that houses some of the NANBIOSIS units, as distributed ICTS, has signed an agreement with MINECO for the co-financing of the Project: “Purchase and installation and set-up of equipment and production and characterization laboratories to complement the units U2-Production of antibodies, U4-Biodeposition and biosensing, U6-Processing of biomaterials and U8-Micro, nanotechnology. The total budget of the project amounts to € 312.800,00 €, with 50% financing with FEDER Funds.
These two projects aim to increase the quantity and quality of the services offered by th implied units, with the objetive of positioning them as national and international benchmark in their respective fields of application. As a consequence, an increase in the performance (number of services and number of users) of each unit is expected, especially from companies (pharmaceutical and small biotechnology).
CSIC and CIBER are processing the necessary contracting procedures for the execution of these projects.
The Fabry International Network (FIN) association established the month of April as the “month of Fabry” to raise awareness and educate about this disease, a rare, progressive and with multi-organ involvement pathology.
Fabry Disease is one of several dozen Lysosomal Storage Disorders that interfere with the body’s ability to break down specific fatty substances. It is a rare disease and because the rate of occurrence is less than 1 in 200,000, it is considered as one of the many “Orphan” diseases. It is more common in women, but it occurs with greater severity in men.
Fabry disease is a metabolic disease that is produced by a deficiency of the ysosomal enzyme Alpha galactosidase. It is transmitted on the X chromosome. Fabry affected patients are missing alpha-galactosidase A (alpha-gal A) which results in sugars and fatty acids (Gb3) accumulating in the cells throughout the body and impairs the function of several major organs including the kidneys and heart. In 2001, enzyme replacement therapy appeared when the alpha-galactosidase protein (alpha- and beta-agalsidase) was synthesized in the laboratory using genetic engineering techniques. This treatment is injected into patients every 15 days to replenish the deficit levels of this enzyme and stop the progression of the disease.
CIBER-BBN, partner of NANBIOSIS, leads the European project Smart4fabry funded by the Horizon 2020 program, which will be developed through a consortium formed by 14 partners from 5 different countries. The CIBER-BBN coordinates the project through the participation of four of its groups that coordinate four units of NANBIOSIS (U1.Protein Production Platform (PPP), U3. Synthesis of Peptides Unit, U6. Biomaterial Processing and Nanostructuring Unit and U20. In Vivo Experimental Platform.) In addition, the consortium is formed by the University of Aarhus (Denmark), Technion Israel Institute of Technology (Israel), Joanneum Research (Austria), Biopraxis Research AIE (Spain), the spin off Nanomol Technologies SL (Spain) ), BioNanoNet (Austria), Drug Development and Regulation SL (Spain), the Covance Laboratories LTD group (UK), and Leanbio SL (Spain) Smart-4-Fabry has been conceived and developed to obtain a new nanoformulation of GLA, that will improve the efficacy and toleration of the treatment with non-formulated GLA. The final benefit will be seen as a considerable reduction on the Fabry disease treatment cost and a substantial improvement in the life-quality of Fabry disease patients.
Fabry International Network, FIN was established in 2005, as a non-for-profit organization registered in The Netherlands. The primary aim of the project is to facilitate collaboration between patient organizations around the world to support those affected by Fabry disease
FIN is connected to over 45 countries around the world. Membership is free and open to any National Patient Organization in which Fabry patients are represented. The National Fabry Disease Foundation – USA, for April 2018 Fabry Disease Awareness Month, have been providing an educational or information post on their Facebook page, every day of the month in April. The NFDF also distributed their My Health Handbook kit and, so far, distributed about 700 kits to individuals with Fabry disease. Fabry Australia have a new website and they are also running a new social media campaign. Fabry Support & Informatie Groep Nederland, FSIGN, since 2005 has organized every first Saturday of April (in the Fabry Awareness Month April) to be the Fabry women’s day. Japan Fabry Disease Patients and Family Association, in awareness month JFA held an open seminar at Fukuoka University Medical hall with lectures on three major topics: Newborn Mass Screening, Current Treatments and Employment and Clinical Genomics. In Spain the Fabry patient organization are the Spanish Fabry MPS Association
The Fabry International Network will cellebrate the 6th Fabry Expert Meeting on
8th – 10th June 2018 at the Vilnius Grand Resort, Ežeraičių g. 2, Ežeraičių km., Avižienių sen., Vilniaus raj., LT-14200, Lietuva.
The European project “Smart-4-Fabry”, is coordinated by CIBER-BBN, specifically by NANOMOL group at ICMAB-CSIC (Dr. Nora Ventosa) and the Biomaterial Processing and Nanostructuring Unit (U6) of ICTS “NANBIOSIS”, and it also counts with the participation of NANBIOSIS Units U1 Protein Production Platform (PPP), U3 Synthesis of Peptides Unit, and U20 In vivo Experimental Platform.
Fabry disease is an inherited genetic disorder of the lysosomal storage group, which affects many organs and parts of the body, as it is caused by the accumulation of a lipid in the lysosomes of the cells, altering their functions and leading to cell death. This accumulation is due to the lack of an enzyme, α-Galactosidase A (GLA). The symptoms are many: limb pains, stains on the skin, problems with sweating, blurred frontal vision, gastrointestinal problems, loss of hearing, etc. In the long term it can cause renal failure, and heart and central nervous system problems.
Patients can lead a normal life with the current treatment called “enzyme replacement therapy”, where GLA is administered intravenously to patients. However, this treatment exhibits several drawbacks, related to a high instability, high immunogenicity or low efficacy of this molecule crossing cell walls. The development of a new treatment for this disease, as well as for other rare diseases, has become a priority challenge within the European program H2020.
Smart-4-Fabry, acronym for “Smart functional GLA-nanoformulation for Fabry disease”, was born with the idea of obtaining a new nanoformulation of GLA that will improve the efficacy and tolerance of the existing treatments. The project will advance from experimental proof of concept, to the preclinical regulatory phase. The ultimate goal is to reduce the treatment cost and to improve the quality of life of patients with Fabry disease.
Smart-4-Fabry, involves the participation of fourteen partners from five different countries from academia and industry. The consortium is formed by: Network of Biomedical Research Centers: Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) with the NANOMOL group at the Institute of Materials Science of Barcelona (ICMAB-CSIC), the Drug Delivery and Targeting Group at the Vall d’Hebron Research Institute (GDLF-VHIR), the Peptide Synthesis Unit at the Barcelona Science Park (UQC-PCB), and the Biotechnology and Biomedicine Institute of the Autonomous University of Barcelona (IBB-UAB) (Spain); Aarhus University (Denmark); Technion Israel Institute of Technology (Israel); Joanneum Research (Austria); Biopraxis Research AIE (Spain); the spin off Nanomol Technologies SL (Spain); BioNanoNet (Austria), Drug Development and Regulation SL (Spain), the Covance Laboratories LTD (UK) group; and Leanbio SL (Spain).
For further information: http://smart4fabry.eu/
The use of In vitro testing with living cells as an alternative to animal research has limitations like the difficulty to reproduce the interaction of cells. To overcome it, scientists are working on the development of systems that simulate and reproduce functions of tissues and organs in conditions very similar to reality. They are called organ-on-a-chip, which include microenvironments and microarchitectures that simulate the state of tissues and living organs.
Scientists of NANBIOSIS Unit 8 have published in an article, cover of the magazine “Lab on a Chip”, the “proof of concept” of a microfluidic device that reproduces the blood-retinal barrier, that is, a microchip that allows us to reproduce what happens ” in vivo ‘in the retina. This device can be an essential tool that revolutionizes experimentation ‘in vitro’.
José Yeste, researcher of the CIBER-BBN, explains that the micro device consists of several parallel compartments, in which different types of cells have been cultivated to emulate the structure of cellular layers of the retina. They are endothelial cells, that is, they form the internal part of the barrier, in contact with the blood capillaries, through which oxygen and nutrients reach the retina. In addition, it is also composed of neuronal cells (which form the neuroretina), and pigment epithelial cells, which constitute the outer layer. The compartments are interconnected in their lower part by a network of micro-grooves, so as to allow an intercellular communication through the exchange of signalling molecules between cells. Thus, cells can send their signals to others and interact, much like they would in a living organism. In addition, the micro device allows the endothelial cells to be subjected to the mechanical stimulus induced by the flow to emulate a more physiological microenvironment.
“Within the body, the endothelial cells that line the inside of blood vessels are subject to the mechanical stimulation of blood circulation. In cell cultures that do not reproduce this flow, the cells are as ‘lethargic’, and do not respond in the same way they would in real conditions, “explains Rosa Villa, Scientific Director of NANBIOSIS Unit 8 and leader of the group of Biomedical Applications of the Microelectronics Institute of Barcelona of the CSIC.
Scientists have evaluated the correct formation of the blood-retinal barrier by performing permeability, electrical resistance tests, as well as protein expression of tight junctions between cells. These tests were intended to verify that the barrier is well formed, that it has closed but maintains the natural permeability, sufficient to allow the passage of nutrients and oxygen, and that the cells are in contact and interact with each other.
This work has been developed in the ICTS NANBIOSIS, more specifically in Unit 8 of Micro-Nano Technology located in the IMB-CNM. It is also part of the results of the CIBER intramural project called Micro BRB: Microfluidic model of retinal neurovascular unit to identify new therapeutic targets in diabetic retinopathy (2016-2017) in wich also participates Unit 3 of NANBIOSIS
Article of reference:
A compartmentalized microfluidic chip with crisscross microgrooves and electrophysiological electrodes for modeling the blood–retinal barrier. Jose Yeste, Marta arcía-Ramírez, Xavi Illa, Anton Guimerà, Cristina Hernández, Rafael Simó and Rosa Villa. DOI: 10.1039/C7LC00795GLab Chip, 2018, 18, 95-105
Researchers of NANBIOSIS U3: Synthesis of Peptides Unit participate in the identification of activators of of the mitochondrial protein Mitofusin 2, a possible therapeutic target for the treatment of patients with type 2 diabetes in collaboration with CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM) and the CIBER of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN).
Those researchers are led by Fernando Albericio (Scientific Director of Unit 3 of NANBIOSIS) at the University of Barcelona and Antonio Zorzano en el IRB Barcelona have identified activators of the mitochondrial protein Mitofusin 2 for the treatment of type 2 diabetes. This protein is expressed at abnormally low levels in the tissues of patients with diabetes. “Thanks to the studies of phenotypic screening and validation studies in human cells, it has been possible to demonstrate the role of the protein Mitofusin 2 in the development of many of the alterations associated with diabetes”, explain those responsible for the work.
These studies have been possible thanks to the work of biologists and chemists from different CIBER areas and with experience in synthetic chemistry, molecular screening and functional analysis.
Article of reference:
Identification of New Activators of Mitochondrial Fusion Reveals a Link between Mitochondrial Morphology and Pyrimidine Metabolism. Miret-Casals L, Sebastián D, Brea J, Rico-Leo EM, Palacín M, Fernández-Salguero PM, Loza MI, Albericio F, Zorzano A. Cell Chem Biol. 2017 Dec 23. pii: S2451-9456(17)30428-2. doi: 10.1016/j.chembiol.2017.12.001.
Last 13 and 14 of November, CIBER-BBN has celebrated its 11th Annual Conference in Hotel Santemar in Santander. In this conference there was a poster session with the participation of the following Units of NANBIOSIS. Special mention deserves Unit 1 with Neus Ferrer as Director and Paolo Saccardo as Coordinator (in the picture):
Posters:
Engineering protein complexes as nano- or micro-structured vehicles or drugs for human and veterinary medicine. Ugutz Unzueta, Naroa Serna, Laura Sánchez-García, José Vicente Carratalá, Olivia Cano-Garrido, Mercedes Márquez, Paolo Saccardo, Rosa Mendoza, Raquel Díaz, Héctor, López-Laguna, Julieta Sánchez, Anna Obando, Amanda Muñoz, Andrés Cisneros, Eric Voltà, Aida Carreño, José Luis Corchero, Neus Ferrer-Miralles, Esther Vázquez, Antonio Villaverde.
Intrinsic functional and architectonic heterogeneity of tumor-targeted protein nanoparticles. Mireia Pesarrodona, Eva Crosa, Rafael Cubarsi, Alejandro Sanchez-Chardi, Paolo Saccardo, Ugutz Unzueta, Fabian Rueda, Laura Sanchez-Garcia, Naroa Serna, Ramón Mangues, Neus Ferrer Miralles, Esther Vázquez, Antonio Villaverde.
Synthesis of different length monodisperse COL-PEG-PEPTIDE to increase biodisponibility of multifunctional nanovesicles for Fabry’s desease. Edgar Cristóbal-Lecina; Daniel Pulido; Solène Passemard; Elizabet González-Mira; Jaume Veciana; Nora Ventosa; Simó Schwartz; Ibane Abasolo; Fernando Albericio and Miriam Royo.
Preclinical behavior of medium-chain cyanoacrylate glue with two different surgical application forms for mesh fixation in abdominal wall repair. Gemma Pascual, Bárbara Pérez-Köhler, Marta Rodríguez, Claudia Mesa-Ciller, Ángel Ortillés, Estefanía Peña, Begoña Calvo, Juan M. Bellón.
Inspiration and Expiration Dynamics in Acute Emotional Stress Assessment. Javier Milagro, Eduardo Gil, Jorge M. Garzón-Rey, Jordi Aguiló, Raquel Bailón.
Poly-DL-lactic acid films functionalized with collagen IV as carrier substrata for corneal epithelial stem cells. Ana de la Mata, Miguel Ángel Mateos-Timoneda, Teresa Nieto-Miguel, Sara Galindo, Marina López-Paniagua, Xavier Puñet, Elisabeth Engel, Margarita Calonge.
Strategy for engineering myoglobin nano-traps for biomedical sensing technology. E. Laukhina, O. V. Sinitsyna, N. K. Davydova, V. N. Sergeev, A. Gomez, I. Ratera, C. Blázquez Bondia, J. Paradowska, X. Rodriguez, J. Guasch, Jaume Veciana.
Structure and nanomechanics of quatsome membranes. B. Gumí-Audenis, L. PasquinaLemonche, J.A. Durán, N. Grimaldi, F. Sanz, J. Veciana, I. Ratera, N. Ventosa and M.I. Giannotti
Bioreceptors nanostructuration study for early detection of Alzheimer. José Marrugo, Dr. Samuel Dulay, Dr. Mònica Mir, Prof. Josep Samitier.
RGD dendrimer-based nanopatterns promote chondrogenesis and intercellular communication for cartilage regeneration. Ignasi Casanellas, Anna Lagunas, Iro Tsintzou, Yolanda Vida, Daniel Collado, Ezequiel Pérez-Inestrosa, Cristina Rodríguez, Joana Magalhães, José A. Andrades, José Becerra, Josep Samitier.
Long-range electron transfer between redox partner proteins. Anna Lagunas, Alejandra GuerraCastellano, Alba Nin-Hill, Irene Díaz-Moreno, Miguel A. De la Rosa, Josep Samitier, Carme Rovira, Pau Gorostiza.
Miniaturized multi-sensing platform for pH and Dissolved Oxygen monitoring in Organ-On-aChip systems. M. Zea, A. Moya, I. Gimenez, R. Villa, G. Gabriel.
Electrochemical characterization of SWCNTs based microelectrodes fabricated by inkjet printing. M. Mass, A. Moya, G. Longinotti, M. Zea, M. Muñoz, E. Ramon, L. Fraigi, R. Villa, G. Ybarra, G. Gabriel.
In vivo imaging and local persistance of polymeric micro- and nanomaterials labelled with the near infrared dye IR820. Isabel Ortiz de Solórzano, Gracia Mendoza, Inmaculada Pintre, Sara García-Salinas, Víctor Sebastián, Vanesa Andreu, Marina Gimeno, Manuel Arruebo.
Cationic nioplexes-in-polysaccharide-based hydrogels as versatile biodegradable hybrid materials to deliver nucleic acids. Santiago Grijalvo, Adele Alagia, Gustavo Puras, Jon Zárate, Judith Mayr, José Luis Pedraz, Ramon Eritja
Perfluorocarbon-loaded Nanocapsules from Nano-emulsion Templates as Microbubble Precursors for Biomedical Applications. G. Calderó, A. González, M. Monge, C. Rodríguez-Abreu, M.J.García-Celma, C. Solans.
Biodistribution study of polymeric drug-loaded nanoparticles in murine model. Marta Monge, Aurora Dols, Stephane Fourcade, Aurora Pujol, Carlos Rodríguez-Abreu, Conxita Solans.
Behavior and a comparative study between tantalum and titanium alloy implant surfaces against bacterial adhesion. M.A. Pacha-Olivenza, M.L. González-Martín.
Bacterial adhesion on calcium ion-modified titanium implant surfaces. M.A. Pacha Olivenza, R. Tejero, M. Delgado-Rastrollo, M.L. González-Martín.
Bioactive coatings to promote tissue regeneration and ingrowth into 3D custom-made porous titanium endoimplants (COATREG-3D). Santos-Ruiz L; Granados JF; Ruiz F; Yáñez JI; González A; Cabeza N; Vida Y; Pérez-Inestrosa E; Izquierdo-Barba I; Vallet-Regí M; Rubio J; Orgaz F; Rubio N; González ML; Peris JL; Monopoli D; Becerra J.
Subcutaneous implantation of a biodegradable apatite/agarose scaffold: biocompatibility and osteogenesis characterization in a rat model. Natalio García-Honduvilla, Gemma Pascual, Miguel A. Ortega, Alejandro Coca, Cynthia Trejo, Jesús Román, Juan Peña, María V. Cabañas, Julia Buján, and María Vallet-Regí.
Dual T1/T2 NCP-based novel contrast agents for brain tumor MRI: a preclinical study. Suarez, S; Arias-Ramos, N; Candiota, AP; Lorenzo, J; Ruiz-Molina, D; Arús, C; Novio, F.
Metronomic treatment in immunocompetent preclinical GL261 glioblastoma: effects of cyclophosphamide and temozolomide. Ferrer-Font, L; Arias-Ramos, N; Lope-Piedrafita, S; Julià- Sapé, M; Pumarola, M; Arús, C; Candiota, AP.
Gated nanodevices for innovative medical therapies. Maria Alfonso, Irene Galiana, Beatriz Lozano, Borja Diaz de Greñu, Cristina de la Torre, Andrea Bernardos, Sameh El Sayed, Daniel MuñozEspin, Miguel Rovira, José Ramón Murguía, Manuel Serrano, Ramón Martínez-Máñez.
NANOPROBE: Gated sensing materials and devices for the detection of infectious diseases and urological cancer. Ángela Ribes, Luís Pla, Sara Santiago-Felipe, Alba Loras-Monfort, M.Carmen Martínez-Bisbal, Elena Aznar, Guillermo Quintás-Soriano, José Luis Ruiz-Cerdá, María Angeles.
Unit 1 of NANBIOSIS, Protein Production Platform (PPP), Unit 3, Synthesis of Peptides, Unit 20, In Vivo Experimental Platform and Unit 6, Biomaterial Processing and Nanostructuring Unit, have jointly developed the research conducted in relation with a CO2-based methodology for the one-step production of protein-nanoliposome conjugates as bio-active nanomaterials with therapeutic interest. The results have been published in Advanced Healthcare Materials: http://www.ncbi.nlm.nih.gov/pubmed/26890358
“a-Galactosidase A Loaded Nanoliposomes with Enhanced Enzymatic Activity and Intracellular Penetration I. Cabrera, I. Abasolo, J. L. Corchero, E. Elizondo, P. Rivera, E. Moreno, J. Faraudo, S. Sala, D. Bueno, E. González-Mira, M. Rivas, M. Melgarejo, D. Pulido, F. Albericio, M. Royo, A. Villaverde, M. F. García-Parajo, S. Schwartz Jr., N. Ventosa,*, and J. Veciana,*
Lysosomal storage disorders (LSD) are caused by lysosomal dysfunction usually as a consequence of deficiency of a single enzyme required for the metabolism of macromolecules such as lipids, glycoproteins and mucopolysaccharides. For instance, the lack of alpha-Galactosidase A (GLA) activity in Fabry disease patients causes the accumulation of glycosphingolipids in the vasculature leading to multiple organ pathology.
Enzyme replacement therapy (ERT), which is the most common treatment of LSD, exhibits several drawbacks mainly related to the instability and low efficacy of the exogenously administered therapeutic enzyme. In this work, the unprecedented increased enzymatic activity and intracellular penetration achieved by the association of a human recombinant GLA to nanoliposomes functionalized with RGD peptides is reported. Moreover, these new GLA loaded nanoliposomes lead to a higher efficacy in the reduction of the GLA substrate named globotriasylceramide (Gb3) in a cellular model of Fabry disease, than that achieved by the same concentration of the free enzyme. The preparation of these new liposomal formulations by DELOS-SUSP, based on the Depressurization of a CO2-Expanded Liquid Organic Solution, shows the great potential of this CO2-based methodology for the one-step production of protein-nanoliposome conjugates as bioactive nanomaterials with therapeutic interest.
