News

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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Two researchers from NANBIOSIS Unit 27 obtain new European projects “Marie Curie”

The European Union has selected the projects sponsored by two researchers from Unit 27 of NANBIOSIS: Esther Pueyo, with “PIC”, to customize the diagnosis and cardiovascular treatment and Pablo Laguna, with “MY-ATRIA”, to improve the early detection of arrhythmias Cardiac. Both projects include massive calculations that will be executed through unit 27 of NANBIOSIS, High Performance Computing.

“MY-ATRIA” / Mutlidisciplinary and training network for Atrial fibrillation monitoring, treatment and progression “, by Pablo Laguna, Professor of Signal Theory and Communication and researcher of the group BSICoS of I3A and CIBER-BBN and Scientific Director of Unit 27 of NANBIOSIS, will affect the early detection of Atrial fibrillation, since it is one of the most frequent cardiac arrhythmias in the adult population. We will study the cellular electrophysiological analysis that leads to the appearance of the arrhythmias so as to be able to design more efficient drugs and to guide the surgeon efficiently in the surgical interventions of ablation of the arrhythmia with minimal affectation on the atrium.

In this project with 3M euros to train 12 researchers, the group will receive 500,000 euros to hire two young pre-doctoral students.

“PIC- Personalized In-Silico Cardiology”, obtained by Esther Pueyo, a professor and researcher at the I3A at the University of Zaragoza, who holds a ‘Starting Grant’, seeks the development of mathematical and computational tools to model cardiovascular physiology in healthy subjects and patients with cardiovascular diseases and evaluate different forms of therapy.

PIC, which will train 15 researchers, has 3.9M euros, of which 250,000 euros correspond to the BSICoS group, coordinator of Unit 27 of NANBIOSIS. The network is coordinated by King’s College London and involves seven universities from EU countries as well as nine other non-academic organizations, including IBM, Medtronic and Janssen Pharmaceutica, or John Radcliffe Hospital.

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NANOMEDICINE AND FUTURE, explained by Simó Schwartz, Director of U20 of NANBIOSIS.

NANBIOSIS-U20 Scientific Director, Simó Schwartz, speaks about Nanomedicine in an interview publish in http://www.quimicaysociedad.org. NANBIOSIS is an Singular Scientific Technological Infrastructure (ICTS) that provides a complete service for the production and characterization of nanomaterials, biomaterials and systems in biomedicine, including the design and production of biomaterials and nanomaterials and their nanoconjugates, and the characterization of these bio-/nanomaterials, tissues and medicals devices from a physic-chemical, functional, toxicological and biological (including preclinical validation) point of view, focused also on biomedical applications such as: IVDs, biosensors, regenerative medicine, drug delivery, therapeutic agents or MRI contrast agents and medical devices.

Question: First of all, what is meant by nanomedicine?

Answer: Nanomedicine is considered any application of nanotechnology that aims to improve the treatment or diagnosis of a disease. In fact, one of the most important aspects of nanomedicine is to generate drugs with different components whose functions at the nanoscale are different when they are linked to when they are not. This makes the nanomedicines per se have a series of attributions that make, in general, their present use very clear advantages for the treatment with respect to conventional medicines. They are much more effective medicines, focussed on the target cells that are intended to be treated and with many less toxic effects.

For some editions Expoquímia has hosted conferences on this new type of medicine.

Numerous clinical trials are now underway in which the therapeutic efficacy of many nanomedicines is already being tested. Therefore, it is a fast-moving science that is already present in the market. Thus, there are already anti-tumor drugs that are nanomedicines, which have displaced the conventional treatment that was used until recently, for example, in breast cancer. And there are many more that we hope will get into the usual clinical practice in the coming years.

What types of diseases can nanomedicine be applied to? And with what results?

In principle, there is not a single specific prototype of disease in which nanomedicine can be applied or not. Any disease is susceptible of being treated by means of nanomedicine if it is necessary to transport a drug of a specific form to a specific site, reducing the general undesirable effects of medicines and increasing their effectiveness. At the moment, it has been tested that the use of nanomedicines implies a greater therapeutic efficiency to be able to transport more drugs to the places where they are needed and much less to the places to which they should not arrive.

In reality, nanomedicines are drugs that have a specific transport system that makes that medicine instead of circulating freely through the blood is transported in a specific way to a specific site. During that transport, that drug can not act anywhere and, therefore, can not have any kind of adverse effect as if it were for free. And, in this sense, the results are good, as there is more therapeutic indication and much less general toxicity. Thus, in treatments such as cancer, where the drugs are very aggressive and have many adverse effects, nanomedicines compensate in a substantial way.

Do you think that a greater implantation of nanomedicine could eradicate diseases that, today, are incurable?

A disease is incurable because it has no known treatment or because that treatment is not specific enough or has a very narrow efficacy and toxicity index. That is, the therapeutic window is very narrow and per se they are very toxic. In that sense, nanomedicine, by reducing the general toxicity of the drug and being much more specific, can make certain diseases, which today have a low cure rate, improve. But nanomedicine is a specific chemical transport system, which always needs a drug or a molecule, which is the active principle that is, through a mechanism of action determined, to cure that disease. This includes gene therapy.

How can a major use of nanomedicine be encouraged? Is it open to public-private collaboration?

Definitely. Nanomedicines are just new medicines. Therefore, a drug that is effective, based on scientific evidence and medical at the level of clinical practice, will always have a majority use. Consequently, as in any other medicine, public-private collaboration is more than necessary because the amount of investment required to put a nanomedicine in the market is as high as that needed by any other medicine on the market. And today, such partnerships are essential to ensure that these drugs come to term.

Besides the economic aspect, are there other factors that can prevent the expansion of nanomedicine as a treatment?

Like any other medicine, the main problem that nanomedicine has is the high economic cost of its development. It must be borne in mind that it has to go through numerous regulatory phases, demonstrate efficacy and declare that there is no toxicity or an acceptable general toxicity like any other drug. And there the economic aspect is fundamental. In principle, there are no other factors. But it is true that, today, the production process of these nanomedicines is more complicated, since they are formed by several components. And there is no factory that is capable of generating any nanomedicine anywhere. And that is a problem, but at the same time, it represents an opportunity for the pharmaceutical industry.

In this sense, what is the purpose of the Nanomedicine Day that will take place in Expoquimia 2017?

The main objective is to disseminate what nanomedicine represents and means, as well as the therapeutic opportunities it entails,to facilitate the understanding of the difference between a conventional medicine and a nanomedicine, how nanomedicines work and why they are more effective and less toxic and why there is so much interest in developing and using these systems to improve the results of current treatments.

Lastly, shall nanomedicine be the medicine of the 21st century?

Undoubtedly, many diseases will be treated with nanomedicines, since they allow a more effective treatment and with less toxicity.

By Eduard Pérez Moya

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