News

Therapeutic approaches with CRISPR for albinism

Preclinical Development of CRISPR- based non-viral therapeutic approaches in existing cellular and animal models of Albinism, (NanoCripsAlbino Therapy) is a multidiciplinar project to study ways to bring genetic editing tools to target cells to develop therapeutic strategies that can be used to treatment. The project, participated by Lluís Montoliu (CIBERER) and José Luis Pedraz (CIBER-BBN) and will financed by the Internationalization Platform of CIBER-BBN/ER/RES- with € 50000.

José Luis Pedraz is the Scientific Director of NANBIOSIS Unit 10 Drug formulation and PI of the CIBER-BBN NANOBIOCELL group, experst in de development of micro and nanoparticles to formulate new active principles based on peptides, proteins… and coming from new technologies such as Crispr/Cas technology. Specially in this project as Dr. Pedraz explains “We will contribute with our know-how in the development of non-viral particles based on lipid components to attach them to the CRISPR system and release them taking them to the target cell to correct the genetic defect”

Researchers have carried out a video to expose the objectives of the new project.

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Novel synthetic routes as potential multifunctional theranostic nanodevices

Carlos Rodriguez-Abreu, Scientific Director of NANBIOSIS Unit 12 is co-author of the publication “Novel synthetic routes of large-pore magnetic mesoporous nanocomposites (SBA-15/Fe3O4) as potential multifunctional theranostic nanodevices” by “Journal of Materials Chemistry B”.

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Researchers of NANBIOSIS U3 find activators of a possible therapeutic target for the treatment of patients with diabetes and insulin resistance

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.

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ISO 9001:2008 certification of Quality Management System to NANBIOSIS U20

The Area of Functional Validation & Preclinical Research of CIBBIM-Nanomedicine has recently obtained the ISO 9001:2008 certification of Quality Management System.

Functional Validation & Preclinical Research (FVPR), led by Dr. Ibane Abasolo, Scientific Coordinator of Unit 20 of NANBIOSIS “In Vivo experimental Platform“, was created in 2007 as part of the CIBBIM-Nanomedicine’s technological offer. The objective of FVPR is to provide services to the different research groups of the mother institutions (VHIR and CIBER), as well as to external companies or groups, to evaluate the effectiveness and toxicity of new therapeutic agents or targets, whether they are nanotechnology-based or not. To this end, it has an “in vivo Experimentation Platform with three differentiated sections (i) Experimental Animal Models, (ii) Molecular Imaging, and (iii) Preclinical Histology) and an “in vitro Experimentation Platform.”

The certification audit was carried out in May 2017 by the certification company TÜV Rheinland and the compliance with the standard was reviewed and that a Quality Management System based on continuous improvement was implemented. The certificate has been issued after the certification process already had been reviewed and approved by the head of the certification body. Now, FVPR is already implementing the transition from this ISO9001:2008 to ISO9001:2015, which will be audited in June of this year.

The ISO 9001 Standard is the most widespread Quality Management tool worldwide, with over one million certificates in 175 countries. The main objective of the standard is to increase customer satisfaction through continuous improvement processes. It is designed so that the organizations that apply it can guarantee their ability to offer services that meet the requirements of their customers. This international standard promotes the adoption of a process-based approach when the effectiveness of a quality management system is developed, implemented and improved, based in turn on the PDCA (Plan, Do, Check, Act) continuous improvement cycle.

The main benefits derived from ISO 9001 certification for organizations are: systematization of operations, improvement of internal organization, generation of a higher level of confidence in the internal and external environment, increased competitiveness, guarantee of compliance with legislation and regulations related to products and services, among others

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Improving biomaterials imaging for nanotechnology: rapid methods for protein localization at ultrastructural level

New publication of Tony Villaverde, Scientific Director of Unit 1 of NANBIOSIS acepted by Biotechnology Journal: The preparation of biological samples for electron microscopy is material- and time-consuming because it is often based on long protocols that also may produce artifacts. Protein labeling for transmission electron microscopy (TEM) is such an example, taking several days. However, for protein-based nanotechnology, high resolution imaging techniques are unique and crucial tools for studying the spatial distribution of these molecules, either alone or as components of biomaterials. In this paper, we tested 2 new short methods of immunolocalization for TEM, and compared them with a standard protocol in qualitative and quantitative approaches by using four protein-based nanoparticles. We reported a significant increase of labeling per area of nanoparticle in both new methodologies (H=19.811; p<0.001) with all the model antigens tested: GFP (H=22.115; p<0.001), MMP-2 (H=19.579; p<0.001), MMP-9 (H=7.567; p<0.023), and IFN-γ(H=62.110; p<0.001). We also found that the most suitable protocol for labeling depends on the nanoparticle’s tendency to aggregate. Moreover, the shorter methods reduce artifacts, time (by 30 %), residues and reagents hindering, losing, or altering antigens, and obtaining a significant increase of protein localization (of about 200 %). Overall, this study makes a step forward in the development of optimized protocols for thehigh resolution imaging techniques high resolution imaging techniques within new biomaterials.

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Polyurethane and polyurea nanoparticle (PUUa), improves cancer therapy

The national consortium led by the research group of Addressing and Drug Release CIBBIM – Nanomedicine of the Vall d’Hebron Research Institute (VHIR) and led by Dr. Ibane Abasolo, Scientific Coordinataror of Unit 20 of NANBIOSIS, has shown improvement in the effectiveness and specificity of targeted therapy against cancer through the use of polyurethane-polyurea nanocapsules (PUUa), a nanoparticle with a proven targeted release, very useful for drugs with a high level of toxicity and low specificity of distribution. This nanoparticle has been developed by the research section of the Catalan company EcopolTech and Unit 20 of ICTS Nanbiosis has participated in vivo nanoparticle biodistribution assays, following the tissue accumulations of fluorescently labeled nanoparticles by means of the IVIS-Spectrum equipment.

The study was based on the encapsulation of the drug Plitidepsin produced and patented by the Spanish pharmaceutical company PharmaMar SA. This drug, which was found in a marine invertebrate of Mediterranean origin and has proven efficacy in laboratory studies, also has a hydrophobic nature that makes its use in humans difficult. The nanoparticle PUUa, by covering the drug, improves biodistribution and reduces the toxicity of the drug, in addition to dramatically reducing the concentration necessary for its therapeutic function. Thus, it potentially increases the use of Plitidepsin in therapy for several types of cancer.
The nanocapsule is based on a shell made of, an RGD peptide to direct the nanoparticles to tumor cells and other fractions that ensure that the drug is released in environments with a high content of glutathione, a molecule that is found in high concentrations inside the tumor cells. Once inside the cell, the drug content is released and therapeutic function begins, highly effective in glioblastoma, colorectal cancer and breast cancer.

The research and synthesis of this nanocapsule has been carried out in collaboration with the Biomedical Research Institute, the CIBBER-BBN, and the companies Ecopol Tech SL and PharmaMar SA.

The importance of nanomedicine in cancer therapy:
In nanomedicine, a nanocapsule refers to an organic and biodegradable nanometric container that contains other molecules inside it, to be released once they reach their destination. In the case of cancer treatment, nanocapsules contain drugs that are usually hydrophobic and if they are administered naked (or without being wrapped by the nanocapsule), they are vulnerable to detection and digestion by macrophages – which reduces the effective accumulation of the drug in the tumor cells-, in addition to presenting a high toxicity both for the tumor cells of interest and for the healthy cells of the individual. These immunological barriers cause the administration at high concentrations of the drug chosen for the therapy, which leads to the known side effects of chemotherapy and the appearance of resistance.

Encapsulation can solve these problems: it prevents the elimination of drugs by macrophages, they circulate for a longer time through the blood flow, and they have improved permeability and retention. All because they are more specific covers and less toxic to the human body. Some of these nanomedicines are already being used in oncological patients, such as Myocet ™, DaunoXome ™, Depocyt ™, Abraxane ™, Genexol- * PM ™, and more recently, Onivyde ™: and all have improved the survival of cancer patients in a significative way.

And the research goes further, since the CIBBIM – Nanomedicine Pharmacological Surveillance and Release group of the VHIR has been working for ten years to bring the nanomedicines in development closer to patients and is currently working on several European projects in which several studies are being studied. nanoparticles for the treatment of pancreatic cancer, colorectal and breast cancer, Ewing sarcoma and Fabry minority disease.

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Conxita Solans receives the lectureship award of the Japan Research Institute of Materials Technology

Prof. Conxita Solans (Nanostructured liquid characterization unit 12 of NANBIOSIS) received the lectureship award of the Japan Research Institute of Materials Technology from Prof. Masahiko Abe, Director of the Institute. Prof. Solans delivered her lecture during the meeting held in Noda (Japan) on December 1st, 2017.

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Graphene transistors as eficient transducers for electrocorticography

Researchers of Micro-Nano Technologies Unit (U8) of NANBIOSIS, are co-authors of a new paper published in Advanced Functional Materials. Neuroelectronic interfaces bridge the central nervous system to the outside world and hold great potential for functional restoration in persons with paralysis, other forms of motor dysfunction, or limb loss. Neuroscientists and neurosurgeons are thus looking for technologies that could ideally record the whole brain with a high spatial and temporal resolution. Electrocorticography (ECoG), the practice of placing arrays of large-diameter electrodes (few millimeters) directly on the cortex is the current clinical solution to obtaining brain recordings with high temporal resolution.

Recent research from the CIBER-BBN and IMB-CNM Biomedical Applications group (IP Rosa Villa) coordinator of NANBIOSIS Unit 8, in collaboration with ICN2 (IP JA Garrido) , IDIBAPS (IP MV Sanchez Vives) and INSERM (IP B Yvert) groups, has focused on the development of graphene technology for electrocorticography. Specifically, flexible graphene transistor arrays have been fabricated and applied to the in vivo measurement of local field potentials.

Graphene is one of the most promising material candidates for neural interfacing thanks to its biocompatibility, low dimensionality and mechanical properties. Additionally, graphene exhibits extraordinary electrical properties such as high carrier mobility and chemical stability, features that only few materials can offer therefore helping to create a very intimate interface between the tissue and the transducing system.

However, previous in vivo studies using single layer CVD graphene have used an electrode configuration. Instead, here they propose the use of a transistor configuration. The main reason for this choice is certainly the local preamplification inherent to a transistor. As a consequence, less environmental noise is picked by the device.

Their work presents a complete description of the fabrication technology, the operation of graphene solution-gated field-effect transistors (SGFET) in saline solution and of the custom characterization electronic system. The devices are finally used in in vivo experiments in which the transconductance and noise are first characterized during slow-wave activity followed by the recording of visual and auditory evoked activity as well as of synchronous activity in a rat model of epilepsy. An in-depth comparison of the signal-to-noise ratio of graphene SGFETs with that of platinum black electrodes confirms that graphene SGFET technology is approaching the performance of state-of-the art neural technologies.

Full details of the fabrication, characterization and in vivo performance of the flexible graphene transistor probes can be found in the paper below.

Hébert, C., et al., Flexible Graphene Solution‐Gated Field‐Effect Transistors: Efficient Transducers for Micro‐Electrocorticography. Advanced Functional Materials, 2017.

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The Minimally Invasive Surgery Centre uses HoloLens glasses for medical training and surgical assistance in urology

The Minimally Invasive Surgery Centre, partner of NANBIOSIS, has developed a software platform to apply mixed reality to medical training and surgical assistance. This will enable the creation of new and more realistic scenarios for medical training and improve surgical results.

The Minimally Invasive Surgery Centre (CCMIJU) uses mixed reality technology, by means of the Microsoft’s HoloLens glasses, to help train future healthcare professionals and provide an assistance tool for complex surgeries.

The institution located in Cáceres has begun using the mixed reality glasses, whose technology combines virtual reality with augmented reality, with the aim of developing, on the one hand, a medical training platform for the anatomy of the pelvic floor, and on the other, a tool for surgical assistance during renal tumor resection procedures.

The use of this technology will benefit both medical students and residents, as well as surgeons. For the former, a software application has been developed and integrated in the HoloLens glasses, that will allow them to visualize and interact with the human anatomy of the pelvis -with and without pathologies- both at muscular, vascular, bone and nervous systems levels. This will facilitate its translation to the real medical practice.

As for the surgeons, this technology will provide access to preoperative studies and real 3D models of the patient in the form of virtual holograms, facilitating the surgical planning and assistance during the abovementioned renal interventions.

The software, developed entirely at the CCMIJU, is in its validation phase in operating rooms. For the first time, and using their own 3D anatomical models, this type of technology is being used for training on the pelvic floor anatomy and for surgical assistance in renal tumor resections.

This R&D line arises from public-private cooperation. The CCMIJU’s team, led by Dr. Francisco Miguel Sánchez Margallo, Scientific Director of this institution, consists of engineers and staff of the Interactive 3D Unit of the Centre who work together with the company CIBEX on the development of new surgical applications. This alliance will enable healthcare professionals to use this emerging technology in challenging surgical interventions and carry out more effective and safe surgeries.

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Pablo Laguna New Elevated IEEE Fellow for his contributions to cardiac biomedical signal processing

Pablo Laguna, Scientific Director of NANBIOSIS Unit 27, has recently been appointed as a select member (IEEE fellow) of the Institute of Electrical and Electronics Engineers within the society of Medical Engineering and Biology -IEEE-EMBS-.

The grade of Fellow recognizes unusual distinction in the profession and is conferred only by invitation of the IEEE Board of Directors upon a person with an extraordinary record of accomplishments in any of IEEE’s designated fields of interest, in this case, Dr. Laguna is recognized for his contributions to cardiac biomedical signal processing.

The IEEE-EMBSis the world’s largest international society of biomedical engineers. The 11,000 members of the organization reside in some 97 countries around the world. EMBS provides its members access to people, information, ideas and opinions that are shaping one of the fastest growing fields in science.

Pablo Laguna is Professor of Signal Theory and Communications at the School of Engineering and Architecture (EINA) and group leader of the CIBER-BBN and University of Zaragoza research group BSICoS . His work focuses on the search of non-invasive indexes to predict the risk of arrhythmias, the modeling and simulation of cardiac electrophysiology, the evaluation and quantification of the activity of the autonomic nervous system and the processing and characterization of biomedical signals in respiratory pathologies. He has been Scientific Director of the CIBER-BBN from 2011 to 2015.

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