News

Modulation of intercolumnar synchronization by endogenous electric fields in cerebral cortex with neuroprobes by NANBIOSIS unit 8

The collaboration of NANBIOSIS U8 Micro–Nano Technology Unit of the CIBER in Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN) at the IMB-CNM in the research carried out by scientist of Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Université Paris-Saclay, Centre National de la Recherche Scientifique (CNRS) and ICREA has bien acknowledged in the publication of the results by Science Advances. Rosa Villa and Xavi Illa have been in charge of the fabrication of the probes used, more specifically, neuroprobes were designed and manufactured with 16 Ti / Au microelectrodes (20 / 200nm) on flexible polyimide substrates with open areas to improve neuronal tissue viability according to specifications.

Abstract

Neurons synaptically interacting in a conductive medium generate extracellular endogenous electric fields (EFs) that reciprocally affect membrane potential. Exogenous EFs modulate neuronal activity, and their clinical applications are being profusely explored. However, whether endogenous EFs contribute to network synchronization remains unclear. We analyzed spontaneously generated slow-wave activity in the cerebral cortex network in vitro, which allowed us to distinguish synaptic from nonsynaptic mechanisms of activity propagation and synchronization. Slow oscillations generated EFs that propagated independently of synaptic transmission. We demonstrate that cortical oscillations modulate spontaneous rhythmic activity of neighboring synaptically disconnected cortical columns if layers are aligned. We provide experimental evidence that these EF-mediated effects are compatible with electric dipoles. With a model of interacting dipoles, we reproduce the experimental measurements and predict that endogenous EF–mediated synchronizing effects should be relevant in the brain. Thus, experiments and models suggest that electric-dipole interactions contribute to synchronization of neighboring cortical columns.

Article of refrence:

Modulation of intercolumnar synchronization by endogenous electric fields in cerebral cortex. Beatriz Rebollo, Bartosz Telenczuk, Alvaro Navarro-Guzman, Alain Destexhe and Maria V. Sanchez-Vives Science Advances 03 Mar 2021: Vol. 7, no. 10, eabc7772 DOI: 10.1126/sciadv.abc7772

• Read More

Simo Schwartz: new General Director of the Bank of Blood and Tissues of Catalonia.

Simó Schwartz Jr., Scientific Director of NANBIOSIS Unit 20 In Vivo Experimental Platform has been appointed as the new general director of the Bank of Blood and Tissues of Catalonia, replacing Enric Argelagués, who is leaving his post after 17 years as director. Argelagués was the promoter of the unification of blood banks that began in the eighties and culminated in the current Bank of Blood and Tissues of Catalonia.

Simó Schwartz now assumes the executive management of the organization, which currently has more than 800 workers and its mission is to ensure that all people in Catalonia have the blood and tissues necessary for their treatment at their disposal, promoting proper use. It is a reference center in diagnostic immunology and in the development of advanced therapies, it is present in the main hospitals in Catalonia and is part of the national and international organizations related to donation, transfusion and treatments with biological components.

• Read More

Reversing pulmonary fibrosis has been achieved in murine models with peptide-loaded nanoparticles

A new study with participation of NANBIOSIS Unit 10 Drug Formulation unit of CIBER-BBN and UPV/EHU, has succeeded in preventing and reversing pulmonary fibrosis in experimental models with PLGA / PEI nanoparticles loaded with the GSE4 peptide. These results are the first step to study its possible antifibrotic effect in patients with idiopathic pulmonary fibrosis and other progressive fibrosing diffuse interstitial lung diseases that present altered telomere function.

NANBIOSIS unit 10 has been responsible for the design and manufacture of biodegradable nanoparticles loaded with the peptide.

The work is led by Rosario Perona and Leandro Sastre, researchers of CIBERER at the Biomedical Research Institute (CSIC/UAM), and Maria Molina-Molina, researcher at CIBERES and the Department of Pulmonology at the Bellvitge University Hospital. In addition, Guillermo Güenechea, from CIBERER at CIEMAT-IIS / FJD, and José Luis Pedraz, from CIBER-BBN and the University of the Basque Country have collaborated.

Idiopathic pulmonary fibrosis is a fatal fibrotic disease associated with aging with a median survival of 2 to 5 years. The disease usually appears around the age of 60, but there are familiar forms that can manifest at younger ages. Fibrosis appears as an aberrant healing response after alveolar damage and is characterized by the appearance of abnormal lung scarring, in which the restoration of epithelial integrity and tissue function is compromised. The mechanisms responsible for defective repair and regeneration are not well understood. However, recent studies suggest a possible role of accelerated aging and telomere shortening in the onset of the disease, mainly in familial forms.

The GSE4 peptide, of 11 amino acids, corresponds to an internal sequence of dyskerin, a protein that is part of the telomerase complex. GSE4 has protective effects on the cells of patients with the rare diseases dyskeratosis congenita and ataxia-telangiectasia, as it increases telomerase activity and cell growth and reduces DNA damage, oxidative stress and cell senescence.

The authors of the study, published in The FASEB Journal, used rat lung alveolar cells treated with a profibrotic agent, bleomycin, as a model. Expression of the GSE4 peptide or treatment with GSE4-PLGA / PEI nanoparticles causes a reversal of the inflammatory and fibrotic phenotype. There is an increase in telomerase activity, a decrease in DNA damage, and a decrease in inflammation and cell death. Furthermore, these cells show an inhibition in fibrosis.

In a rat model with bleomycin-induced pulmonary fibrosis, treatment with GSE4-PLGA / PEI nanoparticles has also increased telomerase activity and decreased DNA damage in alveolar cells. In both preventive and therapeutic protocols, GSE4-PLGA / PEI nanoparticles have prevented and attenuated lung damage and inhibited fibrosis. Histological analysis of the lungs of rats treated with bleomycin and GSE4-PLGA / PEI nanoparticles shows less fibrosis and inflammation and greater regeneration of the alveolar tissue, indicating the therapeutic efficacy of GSE4-loaded nanoparticles in this experimental pulmonary fibrosis model. .

This study supports the possibility of further investigating a potential curative treatment for patients with pulmonary fibrosis.

Reference article:

Pintado-Berninches, L., Montes-Worboys, A., Manguan-García, C., et al. “GSE4-loaded nanoparticles a potential therapy for lung fibrosis that enhances pneumocyte growth, reduces apoptosis and DNA damage.” The FASEB Journal. 2021; 35: e21422. DOI: 10.1096/fj.202001160RR

(*) Explanation of the figure: Treatment with the profibrotic agent bleomycin decreases the number of cells that express the alveolar marker proSP-C (Bleo). Inoculation of GSE4-loaded nanoparticles into bleomycin-treated rats increases the number of cells expressing the marker, indicating alveolar regeneration.

• Read More

Graphene sensors read low-frequency neural waves associated with distinct brain states

Xavier Illa, Anton Guimrea y Eduard Masvidal, researchers of the CIBER-BBN group GAB Lab at IMB-CNM led by Rosa Villa, are coauthors of a study recently published in “Nature Communication”, in which it is demonstrated that graphene-based active sensor arrays are a mature technology for large-scale application in wide frequency band neural sensing interfaces. NANBIOSIS U8 Micro– Nano Technology Unit has been used in the development of the research.

This research has been carruied out within the framework of the European Project “Graphene Flagship. The scientists have developed a sensor based on CVD graphene that detects brain signals in a wide frequency band, from extremely low frequencies to high frequency oscillations. The sensor is biocompatible and could be used to measure and predict brain states. Furthermore, the graphene sensors could be used in chronic implants due to their high stability in the brain.

Further information: News by the Graphene Flagship website.

Article of reference:

Garcia-Cortadella R, Schwesig G, Jeschke C, Illa X, Gray AL, Savage S, Stamatidou E, Schiessl I, Masvidal-Codina E, Kostarelos K, Guimerà-Brunet A, Sirota A, Garrido JA. Graphene active sensor arrays for long-term and wireless mapping of wide frequency band epicortical brain activity. Nat Commun 12, 211 (2021). https://doi.org/10.1038/s41467-020-20546-w

• Read More

CCMIJU leads an European Project based on mixed reality and 3D printing applied to medical education

The CCMIJU, partner of NANBIOSIS leads a European consortium of 9 partners from Spain, Norway, Netherlands, Romania and Greece to carry out the Research Project entitled “Mixed Reality in Medical Education Based on Interactive Applications“-MIREIA, funded by the Erasmus+ Programme – Key Action 2 (KA2): Cooperation for innovation and the exchange of good practices – Knowledge Alliances.

The consortium members will work together to develop an innovative methodology and tools to provide paedagogical content for customized training based on 3D models, such as anatomical models (with and without pathologies) built from real-patient cases (e.g. medical imaging studies) or virtual scenarios for basic training in minimally invasive surgery.

MIREIA will allow health professionals to train in virtual environments or physical simulators based on personalised 3D printed models. Mentors will also be able to create and share their clinical experience.

The Project leader Francisco Miguel Sánchez Margallo, Assistant Director of NANBIOSIS and Scientific Director of the CCMIJU, will be supported by a team of researchers and communication assistants led by Dr. Juan Alberto Sánchez Margallo, researcher in the Bioengineering and Health Technologies Department to carry out the research in cooperation with the rest of the consortium members.

Over a period of 3 years and with a budget of 1M€, the MIREIA Project aims to bridge the gap between classroom learning and laboratory training and actual clinical practice.

• Read More

A more effective nanomedicine has been developed for the treatment of Fabry rare disease.

28 February: International Rare Disease Day

This is one of the major achievements of the European Smart4Fabry project, which is now coming to an end after four years of work.
The results have been made possible by nanotechnology and the approach developed could be applied to other drugs in the future.
The new drug improves on current treatments and helps reduce costs and improve patients’ quality of life.

Barcelona, 26 February 2021.- The advance of nanomedicine opens up new possibilities in the development of drugs, such as the one recently developed for the rare disease Fabry, with improved efficacy compared to existing authorised treatments.

Thus, the European Smart4Fabry project has come to an end with one of the best results possible: the designation of a new orphan drug by the European Commission and the possibility of making progress in the treatment of Fabry, a rare disease that is estimated to affect approximately 2.6 out of every 10,000 people in the EU.

It is a chronic debilitating disease due to recurrent episodes of severe pain that is difficult to control with conventional analgesics, and it is life-threatening due to renal failure and associated cardiovascular and cerebrovascular complications.

“With this designation we have made a major achievement, not only for Fabry patients, but also for other pathologies that can benefit from this same approach, made possible by nanotechnology,” explained Nora Ventosa, Scientific Director of NANBIOSIS Unit 6 Biomaterial Processing and Nanostructuring Unit of CIBER-BBN and ICMAB-CSIC who coordinated the project.

Need for new treatments for the disease

This disease, also known as Anderson-Fabry disease, represents the most common lysosomal storage disorder. It is caused by an absence or deficiency of the enzyme α-galactosidase A (GLA), which results in the lysosomal accumulation of globotriaosylceramide (Gb3) and its derivatives in the lysosomes of a wide variety of tissues, responsible for the clinical manifestations. Current treatments consist of intravenous administration of the GLA enzyme, but have limited efficacy and poor biodistribution.

The drug that has been developed is a new nanoformulation of GLA (nanoGLA) that improves efficacy compared to the reference treatment with non-nanoformulated GLA. “The third-generation liposomal product we have developed in the project has demonstrated, at preclinical level, improved efficacy, compared to authorised enzyme replacement treatments, demonstrating that the strategy of supplying the affected cells with the GLA enzyme via the smart nanoliposome is highly successful”, explained Ibane Abasolo, Scientific Coordinator of NANBIOSIS U20 of CIBER-BBN and VHIR, who is responsible for the efficacy studies in the project.

The nanoGLA product was obtained using DELOS^TM formulation technology, an innovative platform for the robust production of nanomedicines in an efficient and sustainable manner.

The Committee for Orphan Medicinal Products, the European Medicines Agency’s (EMA) committee responsible for recommending orphan designation of medicines for rare diseases, has considered these results to have a clinically relevant advantage over current enzyme replacement therapies.

The designation of orphan drug, in addition to recognising the significant benefit of the new nanomedicine over products already licensed for Fabry disease, has important implications for the translation of the new therapeutic product from bench to bedside.

Those responsible for these results, including several CIBER-BBN groups, highlight that the new formulation helps to improve treatments, reduce costs, and improve the quality of life of Fabry patients.

Interdisciplinarity and public-private collaboration

The Smart4Fabry project has been running since 2017 thanks to European funding of €5.8 million, from the Horizon 2020 programme. This was possible thanks to the collaboration of several CIBER-BBN groups and NANBIOSIS Units at the Institute of Materials Science of Barcelona (ICMAB-CSIC) with the abouve mentioned NANBIOSIS Unit 6, the Institute for Advanced Chemistry of Catalonia (IQAC-CSIC) with NANBIOSIS Unit 3 of
Synthesis of Peptides Unit, led by Miriam Royo, the Vall d’Hebron Research Institute (VHIR) with NANBIOSIS Unit 20 and the Institute of Biotechnology and Biomedicine of the Autonomous University of Barcelona (IBB-UAB) with NANBIOSIS Unit 1 Protein Production Platform (PPP), whose work in this project was led by José Luis Corchero. It has also been necessary to contribute knowledge from different academic and business disciplines.

The project consortium also includes public institutions such as the University of Aarhus (Denmark), Technion Israel Institute of Technology (Israel) and Joanneum Research (Austria); and the companies Biokeralty (Spain); Nanomol Technologies SL (Spain); BioNanoNet (Austria), Drug Development and Regulation SL (Spain), the Covance Laboratories LTD group (UK) and Leanbio SL (Spain), which have provided the necessary expertise in nanotechnology and biotechnology, physicochemical characterisation, in vitro and in vivo biological evaluation, formulation and grading of nanomedicines, and pharmaceutical development and production under the guidelines of regulatory agencies.

CIBER and CSIC, promoters of orphan drugs

Orphan Drug Designations (ODDs) seeks to facilitate the arrival of treatments for rare diseases on the market. Several incentives are associated with ODDs, such as market exclusivity, fee reductions and specific scientific advice.

To date, CIBER has promoted eleven orphan drugs designated by the EMA, mainly from the thematic area of Rare Diseases (CIBERER), this being the first from CIBER-BBN.

On the other hand, this is the fourth ODD that the CSIC has obtained, and the first time it refers to a nanoformulated drug.

Orphan drug designation by the European Medicines Agency has several advantages, such as receiving a commercialisation authorisation for 10 years during which similar products cannot be commercialised, the availability of free or low-cost scientific advice and support protocols, and exemption from designation fees. In addition, entities developing orphan drugs have access to specific grants from the European Union and member states’ programmes.

More information

Scientific Culture Unit UCC+i CIBER cultura.cientifica@ciberisciii.es

Other related news

Smart-4-Fabry final workshop

Rare diseases Day February 29: combating Fabry Disease

Fabry disease & Smart4Fabry project

Lysosomal Rare Disorders: Focus on Fabry Disease

Fabry disease awareness month, April

“a-Galactosidase A Loaded Nanoliposomes with Enhanced Enzymatic Activity and Intracellular Penetration”

• Read More

An Auristatin-based nanoconjugate reduces leukemia burden in a disseminated AML model

Researchers of the Nanotoxicology Unit of the the CIBER-BBN ICTS NANBIOSIS (u18-nanotoxicology-unit), leaded by Ramon Mangues and Isolda Casanova at the Research Institute of the Hospital de Sant Pau and of the NANBIOSIS (nanbiosis.es) Protein Platform (u1-protein-production-platform-ppp) leaded by Antonio Villaverde and Neus Ferrer Miralles of the Institute of Biotechnology and Biomedicine at the Autonomous University of Barcelona, have developed a novel protein-Auristatin nanoconjugate that specifically targets CXCR4-overexpressing acute myeloid leukemia (AML) cells. It selectively accumulates in target cancer cells expressing this receptor and deliver the toxin Auristatin within their cytosol. There, Auristatin potently blocks microtubule polymerization, provoking mitotic catastrophe, followed by apoptotic induction. Since Auristatin can kill both cycling and quiescent cells, the administration of the nanoconjugate at repeated dosage is able to dramatically reduce the leukemia burden in circulating blood, bone marrow, liver and spleen; thus, producing a potent antineoplastic effect, in the absence of systemic toxicity.

It is known that CXCR4 overexpression is involved in bopne marrow colonization by leukemic cells, displacing normal hematopoietic stem cells, an effect that associates with quiescence, resistance to classical chemotherapy, development of minimal residual disease and relapse, which leads to shorter patient survival. Therefore, this Auristatin-based nanoconjugate could be a novel approach for the treatment of CXCR4-overexpressing AML that relapses after classical chemotherapy, offering hope to an effective clinical translation and industrial transfer, aqn activity that which could increase the effectiveness of AML treatment while reducing the adverse effect associated with current therapy.

Reference:

Pallarès V, Unzueta U, Falgàs A, Sánchez-García L, Serna N, Gallardo A, Morris GA, Alba-Castellón L, Álamo P, Sierra J, Villaverde A, Vázquez E, Casanova I, Mangues R. An Auristatin nanoconjugate targeting CXCR4+ leukemic cells blocks acute myeloid leukemia dissemination. doi: 10.1186/s13045-020-00863-9.

• Read More

New COVID-19 Diagnostic System Ready for Trials in Clinical Samples

The new system for the rapid, economic and efficient diagnosis of COVID-19 devised by the Universitat Politècnica de València (UPV), the IIS La Fe and the CIBER-BBN is now ready for trials on clinical samples. Since the pandemic broke out, the group of Professor Ramón Martínez Máñez, a researcher at the IDM Institute of the UPV and scientific director of the CIBER-BBN and NANBIOSIS U26 RNM for Biomedical Applications I, has been working on an alternative for the diagnosis of COVID-19, based on nanoporous films. These materials are capable of storing an indicator that is released only in the presence of the SARS-CoV-2 virus thanks to a system of molecular gates. And they do it very quickly, reliably and easily.

The material has already demonstrated its ability to detect the Spike protein present in SARS-CoV-2 and also its function for the detection of a model virus that expresses the aforementioned protein and that has been implemented by the Viral Biology group of the I2SysBio, center mixed of the University of Valencia and the Higher Council for Scientific Research (CSIC), led by Dr. Ron Geller.

“These advances represent another step towards obtaining the final device and confirming that the system is capable of recognizing virus particles”, highlights Ramón Martínez Máñez, director of NANBIOSIS U26 NMR for Biomedical Applications I.

The UPV team of researchers will carry out the clinical validation of the device in collaboration with Dr. Javier Pemán and Dr. Mª Ángeles Tormo, from the Serious Infection Research Group at IIS La Fe, by Dr. María Dolores Gómez, Head of the Molecular Microbiology Unit of the Microbiology Service of the Hospital Universitari i Politècnic La Fe and by Drs. Miguel Salavert and Eva Calabuig, of the Infectious Diseases Unit of the aforementioned hospital.

Once its sensitivity for the diagnosis of COVID-19 has been verified, it is planned to develop a final kit and obtain the CE marking, which will allow its commercialization. “We hope that this process will be carried out as quickly as possible and that it may be on the market to provide a new tool in the face of the pandemic that we are suffering,” says Dr. Elena Aznar, a researcher at CIBER-BBN.

Among the advantages of the device devised by the researchers of the UPV, UV, CSIC, IIS La Fe and CIBER-BBN, I would highlight its ease of use, being able to be used for the diagnosis of COVID-19 in places with limited infrastructure. Furthermore, it does not require highly qualified personnel and the sample does not have to be analyzed in specialized laboratories.

“In addition, the POC technologies on which it is based are global detection tools to monitor for possible new outbreaks in the future, so that once it is ready for use, it will contribute to the rapid implementation of containment measures”, he highlights Ramón Martínez Máñez.

The development of this project is financed by funds from the Covid-19 Donations of the Generalitat Valenciana, made by people and companies during 2020 to contribute to the fight against the pandemic. The solidarity of the Valencian citizenship materialized in donations of about 1 million euros, destined entirely to research projects of excellence against the virus such as the one led by Professor Martínez Máñez, managed by the Ministry of Innovation, Universities, Science and Society Digital.

The project also has the support of the Supera COVID-19 Fund, promoted by Crue Universidades Españolas, Banco Santander -through Santander Universidades- and the CSIC. In addition, the I2SysBio Viral Biology group (UV-CSIC) received funding from the Valencian Innovation Agency (AVI) for the implementation of the model virus.

A nanotoxin targeting the receptor CXCR4 blocks lymphoma dissemination

Researchers at the Nanotoxicology Unit of CIBER-BBN ICTS NANBIOSIS (u18-nanotoxicology-unit), led by Ramon Mangues and Isolda Casanova of the Research Institute at the Hospital de Sant Pau and the Researchers of the NANBIOSIS (nanbiosis.es) Protein Production Platform (u1-protein-production-platform-ppp) led by Antonio Villaverde and Neus Ferrer Miralles of the Institute of Biotechnology and Biomedicine at the Autonomous University of Barcelona, have participated in the development of a novel protein nanoparticle that incorporates the Exotoxin of the bacteria Pseudomonas aeruginosa, capable of targeting lymphoma cells that overexpress the CXCR4 receptor.

They internalize selectively in target cancer cells through CXCR4 receptor-mediated endocytosis due to the incorporation in its nanostructure of the T22 peptide ligand, with multivalent display (10 peptides per nanoparticle). In addition, it contains an endosomal escape domain to avoid lysosomal degradation to achieve the delivery of undegraded exotoxin in the target cancer cell cytosol. There, the exotoxin blocks protein translation by inhibiting the elongation factor 2, leading to the induction of apoptosis in a diffuse large B-cell lymphoma model blocking their dissemination throughout the body, in the bone narrow, lymph nodes and the liver. Since lymphoma cells overexpressing the CXCR4 receptor are associated with increased dissemination and resistance to Rituximab plus CHOP chemotherapy, this novel nanomedicine could be useful for its clinical translation, especially for the treatment of lymphoma patients that relapse after classical chemotherapy.

The bioluminescent follow-up of cancer cells and toxicity studies has been performed in the ICTS NANBIOSIS using its CIBER-BBN Nanotoxicology Unit Protein production has been also performed at the ICTS NANBIOSIS Init 1 PPP

Reference:

Falgàs A, Pallarès V, Serna N, Sánchez-García L, Sierra J, Gallardo A, Alba-Castellón L, Álamo P, Unzueta U, Villaverde A, Vázquez E, Mangues R, Casanova I. Selective delivery of T22-PE24-H6 to CXCR4+ diffuse large B-cell lymphoma cells leads to wide therapeutic index in a disseminated mouse model. doi: 10.7150/thno.43231. eCollection 2020.

• Read More

Gels formed from the interaction of lipid vesicles: Influence of charge in their structural and rheological properties

Susana Vilchez, researcher at NANBIOSIS U12. Nanostructured liquid characterization unit of CIBER-BBN and IQAC-CSIC, is coauthor of an article recently published in the Journal of Molecular Liquids.

“This work – explains Susana Vilchez – shows how structural and viscoelastic properties of a lipid colloidal gel can be altered by varying the ratio of charged lipids in the dispersion. These findings corroborate that the eventual formation of the gel and the morphology of its network is governed by the repulsive potential of the particles instead of the molecular composition of their membranes. Thus, the right control of charge balance in the system may allow finding specific applications for such material, especially in the biomedical field due to its lipid composition”.

Rheological measurements have been performed by the Nanostructured Liquids Unit (U12) of the ICTS NANBIOSIS.

Article of reference:

Kirian Talló, Susana Vílchez, Ramon Pons, Olga López. Gels formed from the interaction of lipid vesicles: Influence of charge in their structural and rheological properties. Journal of Molecular Liquids Volume 322, 15 January 2021, 114957 https://doi.org/10.1016/j.molliq.2020.114957

• Read More

You are here : Home / News (Page 22)