News

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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Nanoparticles capable of bi-directional communication

The results of a research co-led by Ramón Martínez-Máñez, Scientific Director of Unit 26 of NANBIOSIS and CIBER-BBN have been published by Nature Communication last May 30th, showing how to prepare a nanoparticles chemical communication system using lactose. So far, his group had managed to establish communication between three nanoparticles but only in a unidirectional way. “We have managed to get a nanoparticle to send a chemical messenger to the second nanoparticle, who understands the message and sends another chemical messenger back to the first one. Upon receiving it, it performs an action, in this case releasing a dye,” explains Martínez-Máñezto Efefuturo.

This is a very important “basic” research due to the lack of proven results at the nanoscopic level. This research is the first step in getting the nanoparticles to work in a collaborative and coordinated way, anticipating a future of intelligent nanoparticle networks and advanced controlled release systems, drugs or complex systems based on nanotechnology.

The characterization of the system has been done with NMR unit of NANBIOSIS

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NANBIOSIS at the VI Conference of Young Researchers

On June 2, the VI Conference of Young Researchers organized by the I3A at the University of Zaragoza was held, aimed at doctoral students who have as director or co-director an I3A member.

The inaugural lecture was given by José Antonio Sanz Herrera (Professor Contractor Doctor at the University of Seville and who held his doctorate at I3A) who has talked about Multidisciplinary Research as the basis of the young professor in engineering.

After the inaugural conference a first block was opened with four oral presentations, giving way to the poster session and coffee. A second and final block with four oral presentations will be held next.

One of the presentations has been made by the research group that coordinates Unit 13 of NANBIOSIS with the title “3D simulation of intraestromal ring implants for the stabilization of keratoconus“. Another of the presentations “Heart Rate Variability Analysis in Risk of Asthma Stratification” was in charge of the Coordinating Group of Unit 27 of NANBIOSIS.

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DHA and l-carnitine loaded chitosan hydrogels as delivery systems for topical applications

The journal JCR Colloids and Surfaces A: Physicochemical and Engineering Aspects, has recently publish and interested article which show the results of the research lead by Jordi Esquena, Coordinator of Unit 12 of NANBIOSIS,.

The formation of biocompatible hydrogels of chitosan crosslinked with genipine deposited on textile substrates has been studied and the incorporation and release of active ingredients for cosmetic applications has been investigated. The active principles studied have been dihydroxyacetone (DHA), which produces a sunless tanning effect; And carnitine, used as anti-cellulite agent. The results have shown that crosslinking with chitosan allows controlling the release rate of the active ingredients, slowing the release by increasing the degree of cross-linking. On the other hand, it has been observed that the active principle influences the gelation and the rheological properties of the hydrogels, mainly due to the interactions of the molecules with the amino groups of the chitosan. These results have illustrated the possible use of chitosan hydrogels in cosmetic and cosmetotextile applications. For this study, techniques available on the NANBIOSIS-ICTS have been used.

For further information

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Nanomedicine versus free drug: greater efficiency and less toxicity

The EU-NCL network will finance a project of nanomedicine for prostate cancer cordinated by Simó Schwartz and Ibane Abasolo, NANBIOSIS-U20 Director and Coordinator.

The European Nanomedicine Characterisation Laboratory (EU-NCL) has selected a project from VHIR intended to develop a therapeutic nanoconjugate that improves the treatment of prostate cancer. Among all proposals presented to EU-NCL, only this one in Spain is part of a small group chosen to carry out the necessary tests to move the product into clinical practice, which makes Vall d’Hebron Campus a leading nanomedicine hospital with capacity to generate and validate therapeutic nanoconjugates and nanomedicines.

The main difficulty in this field is to have a nanomedicine that meets certain requirements that can make it susceptible to reach clinical trials. “In our case, pre-clinical trials will be made with a polymer that transports therapeutic paclitaxel, a drug for the treatment of breast cancer, pancreas and prostate, which has proven to be a good candidate to reach clinical phases. Nanbiosis helps us in the efficacy/toxicity part in vivo” says Dr. Simó Schwartz Jr.

What has been seen so far is that this therapeutic nanoconjugate is able to carry much more paclitaxel into the tumour whereas its toxicity profiles are much lower as compared to the free drug used in clinical practice.

In animal models of prostate cancer our nanoconjugate is able to avoid the growth of the tumor while deeply reducing metastasis. It has managed to change the average half-life and pharmacokinetics of the drug and to reduce its toxicity.

As a comparison, when given in animals the same amount of free drug, without the nanomedicine, at the second dose, toxicity is so high that trials have to stop. That is to say, that “the difference in toxicity between the therapeutic nanoconjugate and the free drug is abysmal which allows us to make much more aggressive administration regims, that are not feasible with the conventional drug,” insists Dr. Schwartz Jr.

The next step will be to determine which is the maximum dose of administration that we can use. At the moment, we know that when administered three times a week during 4 weeks no toxicity is seen and the therapeutic efficacy is very good. We need to see if this dose regim can be increased to get even more efficacy, as long as toxicity allows it.

“We work with a nanomedicine that is easily scalable, very stable, it can be lyophilisated (reconstituted) very easily and after two years of storage is still in perfect condition,” he highlights. Therefore, for the next year “our goal is that the nanoconjugate may be authorized as an Investigational New Drug (IND) and hence all essays that we have agreed with the EU-NCL are those that the European Medicines Agency (EMA) consider necessary to achieve the IND designation”, concludes.

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