News

NANBIOSIS organizes a forum for researchers and companies. Dates (probably February 2018) and location (probably Madrid) will be announced soon.

The theme of the Forum is INTELLIGENT BIOMATERIALS / FUNCTIONALIZATION AND BIOMEDICAL DEVICES FOR APPLICATIONS IN REGENERATIVE MEDICINE AND DRUG DELIVERY.

The forum is presented through 2 sessions:

• First session: Short interventions of the latest advances and developments in the lines of research developed by the groups and platforms of Nanbiosis and description of the needs and demands of industry in that area. The companies and groups that request it will be able to have about 10 ‘to present their lines of research and / or needs and demands in relation to the thematic of the forum.
• Second session: Bilateral company-group / platform meetings to identify possible collaborations. These meetings will be pre-scheduled on request.

If you are interested in participating, contact Eduard Farré (628.943.198, efarre@arvor-ing.com) or with Jesús Izco (679.490.537, jmizco@ciber-bbn.es).

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II MASTER ON ENDOSCOPY AND MINIMALLY INVASIVE SURGERY IN SMALL ANIMALS (CEyCMI). EXTRAORDINARY DEADLINE FOR ADMISSIONS

A new extraordinary deadline for admissions to the II MASTER ON ENDOSCOPY AND MINIMALLY INVASIVE SURGERY IN SMALL ANIMALS has been set up, from 1^st to 14th September. It is organised in collaboration with the Extremadura University ant takes place in Jesús Usón Minimally Invasive Surgery Centre as affiliated entity, offering 60 ECTS-credits.Necessary requirements include having a Veterinary studies degree and a B1 English Certificate. The Master will be held during the academic calendar 2017-2018, according to the established program, that will promote the interaction with the students via an on-line training platform, the direct contact with professors and experts, as well as offering an open material repository.

The Master consists on 4 hands-on training sessions at the JUMISC’s, an external stage in one of our partners centre and the Master’s degree final project.

Further info: www.ccmijesususon.com/ceycmi2017

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Gold nanoparticles can activate drugs inside tumors

Jesus Santamaría, Scientific Director of Unit 9 of NANBIOSIS has participated in a study that shows the ability of gold nanoparticles to generate in situ potent anticancer drugs from inert molecules thanks to a mechanism of elimination of terminal chemical groups that nanometric gold is able to catalyze. Gold is ideal for this catalytic role due to its high biocompatibility.

These results, published in the journal Angewandte Chemie, offer new hope in the fight against cancer and have been obtained thanks to the collaboration of scientists of Unit 9 of NANBIOSIS and, Víctor Sebastián, Silvia Irusta and Jesús Santamaría, with researchers from the Center for Cancer Research at the University of Edinburgh, led by Dr. Unciti-Broceta.

The work reveals the possibility of carrying out catalysis in biological means using tiny particles of gold. These gold nanoparticles, camouflaged in a resin microcapsule implanted in the brain of a zebrafish, have succeeded in catalyzing a chemical reaction generating fluorescent compounds.

Significant practical importance

“The main problem of chemotherapy treatments are the side effects in various organs due to the toxicity of the molecules that are used to fight cancer. For this reason, alternative routes are explored from nanotechnology, for example, transporting drugs to the tumor using nanoparticles or alternative treatments to drugs, such as hyperthermia, elevation of local temperature, obtained with nanoparticles”, says Jesús Santamaría.

The conclusions of this work suggest a different way: the drug would be supplied to the patient in its inert form and only converted to the toxic form locally, thanks to the catalysis of the nanoparticles that a surgeon would implant in the tumor.

Article of reference

Pérez-López, A. M., Rubio-Ruiz, B., Sebastián, V., Hamilton, L., Adam, C., Bray, T. L., Irusta, S., Brennan, P. M., Lloyd-Jones, G. C., Sieger, D., Santamaría, J. and Unciti-Broceta, A. (2017). “Gold-Triggered Uncaging Chemistry in Living Systems”. Angew. Chem. Int. Ed.. doi:10.1002/anie.201708379

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Nanomedicine applied to Dermatology by Almirall, Leitat Technology Center & NANOMOL (NANBIOSIS U6)

NANOMOL (ICMAB-CSIC), a research group member of ICTS “NANBIOSIS”, more specifically of the Biomaterial Processing and Nanostructuring Unit (U6), announced today the launch of Nano4Derm, a research project in collaboration with Almirall, S.A and Leitat Technology Center, focused in nanomedicine applied to treat dermatological diseases. Within the framework of this research project, new innovative formulations containing nanoencapsulated active ingredients will be developed for the topical treatment of inflammatory skin conditions, such as Acne and Psoriasis.

Nano4Derm involves the development and physico-chemical and biological characterisation of nanocapsules containing active ingredients, and the generation of scalable formulation prototypes for manufacturing nanoformulations suitable for clinical trials. These innovative formulations will address current unmet needs and challenges, such as antimicrobial resistance, and provide improved topical treatments for Acne and Psoriasis, in terms of side effects, instability of active ingredients, and skin penetration.

Under the terms of the agreement, ICMAB-CSIC and Leitat research centers will be in charge of developing the different prototypes of nanocapsules containing the active ingredients while Almirall will be responsible for the development of formulations containing the encapsulated actives. Furthermore, Almirall and Leitat will evaluate in preclinical studies both the new nanocapsules and formulations in order to select the best solution to address the unmet medical needs in the topical treatment of Acne and Psoriasis.

This agreement will lead to the development of two types of nanocapsules: Quatsomes and Polymeric Nanocapsules. Quatsomes are lipid nanoparticles with higher colloidal stability than liposomes, which favors the production of high quality, pharmaceutical formulations. They are obtained from the DELOS-SUSP, a technology developed by researchers from the Nanomol group (ICMAB-CSIC) based on the use of supercritical fluids such as CO₂. This technology has advantages over other manufacturing methodologies in terms of homogeneity and scalability, as it replaces the use of organic solvents by green solvents. Polymeric Nanocapsules are developed by the Leitat Technology Center, and provide versatility to the project as they can be designed with different drug release profiles depending on the needs being addressed.

This project is funded by the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) through the announcement of the State Program for R&D&i (2016), orientated to the Society Challenges, modality RETOS-Collaboration 2016, and co-financed by FEDER funds from the European Commission.

About Nanomol (ICMAB-CSIC)

NANOMOL is a research group depending on the Institute of Material Science of Barcelona from CSIC, with wide expertise and recognized excellence in the synthesis, processing and study of molecular and polymeric materials with chemical, electronic, magnetic and biomedical properties. NANOMOL is also a member of Biomedical Research Networking center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) and of the technology transfer network TECNIO from ACC1Ó-Generalitat de Catalunya. The development by Nanomol of the different prototypes of nanocapsules will be performed in the ICTS “NANBIOSIS”, more specifically by the Biomaterial Processing and Nanostructuring Unit (U6) of the CIBER in Bioengineering, Biomaterials & NanomedicIne located at the ICMAB-CSIC.

About Leitat

Leitat is a multisectoral private technological center whose mission is to collaborate with companies and other entities to create economic, social and sustainable value, through R+D+2i projects and technological processes from innovation and creativity. Leitat is a brand of the private entity Acondicionamiento Tarrasense and is recognized by the Generalitat de Catalunya (ACCIÓ) and by MINECO.

The Division of Nanomedicine and nanobiosensors of Leitat develops nanosystems for therapeutic application in order to solve specific problems in safety and, absorption issues and improvement of the efficacy of some API. In addition, related to diagnosis the group develops nanoparticles for specific recognition of analytes for the improvement of the sensitivity and signal amplification of biosensor systems.

The Efficacy and Safety Unit of Leitat also participates in Nano4Derm project, which has extensive experience in the development and application of in vitro models for the toxicological and efficacy evaluation of diverse natural products, from the pharmaceutical, chemical, cosmetics and food industries. In the pharmaceutical sector, the Unit acts as a strategic provider in Drug Discovery and pharmaceutical development processes. In recent years this unit has been involved in the development and biological characterisation of micro- and nano-delivery systems for topical application.

About Almirall

Almirall is a global pharmaceutical company with a strong focus in Dermatology and Aesthetics with the mission of providing valuable medicines and medical devices to you and future generations. Our R&D is focused on Dermatology, with a wide range of programs including key indications. Through our innovative products, agreements and alliances, our work covers the entire drug value chain. Almirall is continually growing as a specialist company in a wide range of skin diseases, in order to cover our customers unmet needs.

Founded in 1943, headquartered in Barcelona, Spain, Almirall is listed on the Spanish Stock Exchange (ticker: ALM) and it has become a source of value creation for society due to its vision and the commitment of its long-standing major shareholders. In 2016, its revenues totaled 859.3 million euros and, with more than 2,000 employees, it has gradually built up a trusted presence across Europe, as well as in the US.

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3D bioprinting applied to cancer diagnostics

Mateu Pla Roca, Scientific Coordinator of Unit 7 of NANBIOSIS /IBEC Core Facilities has won CaixaImpulse funding for his project “3D bioprinted array tissue-like cores: tissue-like controls for cancer diagnostics” (3DBIOcores), which will be carried out in collaboration with Antoni Martinez, head of the histopathology service at Hospital Clinic. CaixaImpulse programme aims to promote technology transfer in science.

The project 3DBIOcores will take advantage of 3D bioprinting to create quality control samples that assure and improve cancer diagnostics. Usually, diagnosis is done by histopathology – the microscopic examination of tissues – and then the biomarkers that are found are quantified. However, histological techniques face some degree of variability that can lead to misinterpretation, and for this reason, such tests require quality control samples to be processed side-by-side with patient samples to verify the final diagnosis.

Currently, hospitals use surplus human tissue which is known to express the required biomarkers as quality control samples, but these are scarce and non-homogeneous, and their use raises ethical issues. Mateu’s project proposes 3DBIOcores as a new source of these essential controls. Taking advantage of 3D bioprinting technology, tissue-like structures containing cell lines with relevant cancer biomarkers will be produced and used as a new source of control samples.

“3DBIOcores will be a real innovation in histopathology analysis, with the potential to have an enormous impact on cancer diagnosis based on the histopathological analysis of biopsies, improving precision in cancer treatment and reducing diagnostic errors,” says Mateu.

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Conflicting evidence for ferroelectricity – New publication in NATURE by scientists of NANBIOSIS

Researchers from Unit 6 of NANBIOSIS, -ICMAB (CSIC)/CIBER-BBN-, in collaboration with others from the Universities of Liège, Mons, Grenoble-Alpes, Parma, Augusburg, Girona and CNR-IOA (SISSA) have published in the journal Nature (G. D’Avino et al., Nature, 547, E9-E10, 2017) an article questioning the presence of ferroelectricity at room temperature in organic charge transfer crystals, generated by supramolecular techniques, previously published in the same journal (Tayi et al, Nature, 488, 485-489, 2012), by a team led by Profs. J. Fraser Stoddart (Nobel Prize for Chemistry 2016) and Samuel I. Stupp of the University of Northwestern.

For more information: D’Avino et al, Nature 547, E9-E10 (13 July 2017). doi: 10.1038 / nature22801

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XI International Workshop on Sensors and Molecular Recognition: System for detection of senescent cells in vivo

The XI International Workshop on Sensors and Molecular Recognition will take place on 6 and 7 July 2017 at the Polytechnic University of Valencia. Scientists of the unit 26 of NANBIOSIS will present the results of the research carried on together with researchers from the Universitat Politècnica de València, CNIO, CIBER-BBN and the University of Cambridge: an innovative system that allows the detection of senescent cells in vivo and without damaging the tissue.

The main objective of cellular senescence is to prevent the proliferation of damaged cells and, at the same time, to trigger tissue repair. However, when the damage persists, or during aging, the tissue repair process is inefficient and the senescent cells tend to accumulate. This accumulation of senescent cells in the tissues affects the tissue functions and accelerates the aging.

“Elimination of senescent cells has been shown to improve a variety of diseases associated with aging, reverses degenerative processes and extends longevity. Therefore, the strategies to detect and eliminate senescent cells have gained great interest in recent years”, explains Manuel Serrano, principal investigator of the CNIO Tumor Suppression Group.

“Chemically speaking, the sensor is composed of a fluorophore bound to a galactose. Senescent cells have the differential property of breaking galactose bonds very efficiently. When the sensor is internalized in a senescent cell this link is broken and this results in a great increase in the fluorescence of the sensor, which is the signal that we detect excited with a laser. However, when the sensor is internalized in a normal (non-senescent) cell, no signal is observed, ” says Ramón Martínez-Máñez, Scientific Director of Unit 26 of NANBIOSIS, CIBER-BBN and IDM-UPV Institute.

The sensor has properties that make it possible to be excited by absorbing two photons, which causes that the energy of the laser used to visualize the tissues is much smaller than the conventional sensors. In addition, two-photon techniques decrease tissue damage and have greater penetrability.

“The sensor was injected intravenously into animals that had been treated with chemotherapy (which produced cellular damage and senescence), with a very selective signal being observed in regions that responded to chemotherapy (and therefore had many senescent cells) . The animals not treated with chemotherapy did not show any signs”, said Beatriz Lozano, researcher at the Interuniversity Institute for Research on Molecular Recognition and Technological Development (IDM) at the Universitat Politècnica de València

The probe, that has been characterized in unit 26 of NANBIOSIS is potentially applicable to other models of senescence. Different research groups have already begun to test the probe with its biological models.

Article of reference:

Beatriz Lozano-Torres, Irene Galiana, Miguel Rovira, Eva Garrido, Selim Chaib Andrea Bernardos, Daniel Muñoz-Espín, Manuel Serrano, Ramón Martínez-Máñez and Félix Sancenón. An OFF–ON Two-Photon Fluorescent Probe for Tracking Cell Senescence in Vivo J. Am. Chem. Soc. DOI: 10.1021/jacs.7b04985

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NANBIOSIS: collaborative research opportunities for groups of CIBER consortia

Last week, Jesús Izco, coordinator of NANBIOSIS, presented to CIBER groups the capabilities of NANBIOSIS and the opportunities for collaboration with the ICTS. From these meetings emerged diverse expressions of interest on the part of the attending researchers.

On June 30, Jesús Izco was invited to present NANBIOSIS in the Annual Scientific Conference of CIBERES. He explained several investigations that are currently being developed in NANBIOSIS and can be applied in the diagnosis and therapy of respiratory diseases, such as the development of physical devices and tests that allow the detection of biomarkers, new protein carriers in the format of nanoparticles capable of recognizing cell receptors and being endocytosed in order to deliver drugs or toxins in target tissues, or non-viral vectors based on niosomes for pulmonary gene therapy (eg cystic fibrosis) by inhalation.

Also, on June 28, Dr. Izco participated in a meeting at the Carlos III Health Institute (Madrid) with the working group on lung cancer of CIBERONC about respiratory tract tumors. Jesús Izco presented both examples of the projects currently under development in the NANBIOSIS units with application to the detection and monitoring of lung cancer, such as PreDICT, and examples of results already published in this scientific area.

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Update of the Map of Unique Scientific and Technical Infrastructures (ICTS) 2017-2020

The updating of the Spanish ICTS Map aims to consolidate this map as a tool for long-term planning and development of this type of infrastructure, updating it according to established criteria, with emphasis on quality and scientific-technical and economic sustainability, prioritizing the continuity Of the installations in operation and those that have viable financing scenarios, implementing it jointly with the Autonomous Communities.

This tool also makes it possible to optimally plan the application of national, regional and European funding, in particular FEDER funds from the programming period 2014-2020, aiming to achieve a stable medium-term funding framework to guarantee the achievement of its objectives.

In order to report on the procedure for updating the ICTS Map, a meeting with the directors of the map in force was held on 22 June at the Ministry of Economy, Industry and Competitiveness, where NANBIOSIS was present as well. The Secretary General of Science and Innovation, Juan María Vázquez Rojas, opened the day welcoming the directors and thanking them for their presence and collaboration. Subsequently, the Deputy Director General of Large Scientific and Technical Facilities, José Ignacio Doncel Morales, explained the procedure for updating the ICTS Map.

Once this updating procedure is completed, it will be the Council of Scientific, Technological and Innovation Policy, after a report from the Advisory Committee on Unique Infrastructures (CAIS) approving the configuration and composition of the new ICTS Map.

Further information

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New methodology for cancer screening paves the way for more targeted treatment options

Laura Lechuga, Scientific Director of Unit 4 of NANBIOSIS, is co-author of a new paper published in Scientific Reports. According to Cesar Huertas, co-author of the article, the Gene expression is the process by which information from a gene is converted into a functional product, such as a protein. It is controlled by a complex regulatory network wherein diverse cellular mechanisms enable the cell to respond to its ever-changing environment. One such mechanism is alternative splicing (AS) of mRNA precursors, a particularly flexible regulatory control point where diverse protein isoforms of differing, even opposing, functions are generated. However, these regulation pathways are not without their tripping points; missteps can occur which can sometimes trigger the onset of serious illnesses, including cancer. The good news is that these missteps are reversible, so if we are able to detect them (and we are), we can develop targeted therapeutic responses to treat their precise origin.

Recent research from the ICN2 an CIBER-BBN Nanobiosensors and Bioanalytical Applications group, coordinator of NANBIOSIS Unit 4, has focused on the specific detection of Fas gene isoforms (Fas567 and Fas57), the aberrant splicing of which gene is implicated in tumour growth. Specifically, the overexpression of Fas57 is known to contribute to cancer aggressiveness, making the expression ratio of mRNA Fas isoforms a potential biomarker for the early diagnosis of cancer.

Their work involved adapting the group’s label-free bimodal waveguide biosensor for use on long mRNA sequences, in order to detect this expression ratio. The similarity between the two isoforms and the fact that they occur only in very low concentrations in cells meant that the new sensor needed to be both highly selective and extremely sensitive, especially given that the demands of cost- and time-effectiveness warranted a device that required no sample pre-amplification stage.

Following exhaustive analysis and optimisation, the group has achieved a multiplexing nanophotonic biosensor that can detect the two Fas isoforms in parallel at concentrations as low as 580 fM, making it potentially the most sensitive amplification-free device for the analysis of alternatively spliced isoforms developed to date.

Taken as a blood test, this sensor promises a far less invasive diagnostic approach than biopsies in the not too distant future. Its ease-of-use, relative low cost and speed (less than 30 minutes) together would make it attractive for routine use not only in cancer screening, but also for monitoring the progression of cancers already detected and/or being treated, and the follow-up of patients in remission.

Full details on how the group’s device was adapted and optimised to this new task can be found in the paper below.

César S. Huertas, Santos Domínguez-Zotes & Laura M. Lechuga. Analysis of alternative splicing events for cancer diagnosis using a multiplexing nanophotonic biosensor. Scientific Reports 7, Article number: 41368 (2017); doi:10.1038/srep41368
https://www.nature.com/articles/srep41368

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