2020 - Nanbiosis

“We need a drastic change in the organization and management of science”

The Jorunal “Redacción Médica” has created an espace call Covid-19 Lessons to gather critical evaluations and recommendations of the most relevant personalities in the health sector, so that the National Health System and the professional and business ecosystem that surrounds it can draw conclusions and face future similar challenges with greater guarantees.

Laura M. Lechuga, Scientific Director of NANBIOSIS U4, from CIBER-BBN at ICN2-CSIC, coordinates CONVAT, one of the projects selected by the European Commission to advance in the knowledge about the Coronavirus, adds her perspective to the document Covid-19 Lessons: “We need a drastic change in the organization and management of science“

According to prof. Lechuga, ·one of the main successes in this crisis has been the intense and excellent dedication of a large part of the international scientific community who, from a multidisciplinary perspective, has tried to contribute their talent and training to make great strides in the knowledge of this new SARS-CoV-2 virus; this crisis has driven this collaboration exponentially. “The rapid mobilization of funds and resources available to scientists has also been (and continues to be) impressive during this crisis. The pandemic has placed before the eyes of all humanity that the greatest values of our society lie in knowledge, training, science and research to face a problem of these dimensions that unfortunately may be repeated in the future.“

As main errors, Laura Lechuga highlights the disconnection between the scientific and political world. “The scientits had contributed its knowledge and rigorous studies to warn of the dangers that lie in wait for us, but it is clear that until now the connection between scientific advice and government policies is extremely weak, not only in our country. country but also internationally”

Possibly, at the national level, our scientific system could have given a faster response if it had been much more robust and competitive and had not been so weakened due to the numerous cuts suffered since the previous crisis and the lack of replacement of researchers. Our research environment, although it is nourished by a lot of talent, is not so much in its own development resources, infrastructures and technologies, so its contribution is being more limited.

There is no doubt that we need a decided investment in science both in terms of human and material resources, and a drastic change in the organization and management of science, which causes our scientists to invest most of their valuable time in requests for funding, resources human and cumbersome administrative justifications, which have little to do with scientific research“.

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New therapy for triple negative breast cancer is successfully tested in preclinical animals

Researchers CIBER-BBN and NANBIOSIS Unit 26, the Príncipe Felipe Research Center (CIPF), the Universitat Politècnica de València (UPV) and the Institut de Recerca Biomèdica (IRB) of Barcelona manage to inhibit tumor growth, reduce metastasis and decrease the toxicity of the antitumor drug Navitoclax in preclinical animal models of triple negative breast cancer (TNBC).

These types of TNBC tumors do not express any of the three receptors involved in most breast cancers (estrogen, progesterone, and HER2), so the most common treatments such as hormone therapy are not viable in these patients.

This new study, led by Mar Orzáez, principal investigator of the CIPF Peptides and Proteins Laboratory and Ramón Martínez Máñez, scientific director of CIBER-BBN, NANBIOSIS Unit 26, member of the CIPF-UPV Joint Unit in Mechanisms of disease and Nanomedicine and researcher at the Interuniversity Institute of Research on Molecular Recognition and Technological Development (IDM) at UPV, shows that a combined treatment of a senescence inducer and a senolytic nanoparticle, selectively removes senescent cells, delays tumor growth and reduces metastasis in a mouse model of aggressive breast cancer.

Until now, the application of senescence inducers represents a successful treatment strategy in patients with breast cancer, although the accumulation of senescent cells in the body can sometimes promote tumor recurrence.

Cell senescence or aging takes place in both physiological and pathological situations. When a cell goes into senescence, it stops dividing and releases substances that cause inflammation.

When an uncontrolled accumulation of these senescent cells occurs, the excess of inflammatory factors can end up damaging healthy cells, thereby contributing to aging, the appearance of pathologies such as diabetes, neurodegenerative diseases or promoting the development of tumors and promoting metastasis.

With this new approach, after the induction of senescence, the cells are eliminated by treatment with a senolytic nanoparticle, and a new therapeutic opportunity opens up to improve the results in patients with breast cancer and a new combined treatment is proposed that may be relevant to other senescence-inducing chemotherapeutic drugs.

The results, published in the Journal of Controlled Release (JCR), offer new therapeutic approaches to advance in later phases and clinical trials and allow different tumor types to be addressed.

Orzáez and Máñez have pointed out that “the induction of senescence in tumors represents an advance in the treatment of cancer, which may be even greater in combination with this type of senolytic treatments that eliminate senescent cells and help reduce metastasis.”

Manuel Serrano from the Institut de Recerca Biomèdica (IRB) in Barcelona has also collaborated in the study.

Article of reference:

Irene Galiana, Beatriz Lozano-Torres, Mónica Sancho, María Alfonso, Andrea Bernardos, Viviana Bisbal, Manuel Serrano, Ramón Martínez-Máñez, Mar Orzáez, Preclinical antitumor efficacy of senescence-inducing chemotherapy combined with a nanoSenolytic, Journal of Controlled Release, Volume 323 https://doi.org/10.1016/j.jconrel.2020.04.045

Sourse of information: CIBER-BBN

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Scientific trends with the participation of NANBIOSIS expertise

Within the series of virtual conferences organized during the months of May, June and July by the Extremaduran office, two researchers of NANBIOSIS are invited speakers: Laura M. Lechuga Gómez, NANBIOSIS Unit 4 Biodeposition and Biodetection Unit (form CIBER-BBN and ICN2-CSIC); and María Coronada Fernández Calderón NANBIOSIS U16 Surface Characterization and Calorimetry Unit (from CIBER-BBN and University of Extremadura)who will talk about technologies at the service of health.

The cycle ’90 minutes for Science, for innovation to bring society closer to the latest scientific trends, starts next Wednesday, May 27, at 5:00 p.m. It will deal with topics such as biomedical research and its influence on the improvement of early diagnosis of diseases (the director of the Department of Immunology and Oncology of the CSIC National Biotechnology Center, Ana Cuenda Méndez, will offer a conference on the role of proteins in inflammatory, infectious and cancer processes, and the engineer in Molecular Biotechnology and principal investigator in the Laboratory of Medical Biotechnology of the Austral University of Chile, Alejandro Rojas-Fernández, will address the generation of nano-antibodies against emerging viruses, such as COVID19), ethics in the face of the challenges of artificial intelligence.

Registration, open and free, can now be formalized on the website of the Office for Innovation.

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NAV-GAL, a new senolytic drug against cancer, on spanish TV

The work carried out by the team of researchers of CIBER-BBN and Politecnic University of Valencia, led by, Ramón Martínez Máñez, Scientific Director of NANBIOSIS U26 NMR: Biomedical Applications II, is highlighted by the Spanish TV.

This team has developed a new drug against lung cancer that, along with other therapies, eliminates cells that have been bottled prematurely without harming healthy ones. The drug has been successfully administered in mice, now it comes the challenge of finding a way to administer it without damaging the patient’s healthy organs, and they propose inserting it into a capsule that would be released only in the intestine, thus preventing it from passing through the stomach even if it was administered orally.

This new drug called Nav-Gal , is part of the drugs called “senolytics”, those that are capable of killing only cancer cells.




Further information here

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“Molecular probes and gated materials in biomedical applications and communication between nanoparticles” by Ramón Martínez

Next June 8, 2020, 12 pm, Ramón Martínez Máñez, Scientific Director of CIBER-BBN and NANBIOSIS U26, give an on line seminar, hosted by Jaume Veciana and Anna Roig will from ICMAB-CSIC.

The development of optical molecular probes and probes based on gated nanoparticles has been an area of interest during the last decades. Optical probes are able to transform chemical information in the environment into a suitable optical signal, usually a change in colour of fluorescence. Moreover, gated materials have also been widely used for the development of drug delivery systems.

Some examples of optical probes and gated materials for sensing and controlled delivery in biomedical applications will be described. From another point of view, the talk will also describe how nanoparticles are able to communicate each to another via the exchange of chemical messengers. Communication between nanodevices may find applications in different areas and a number of future new results are envisioned in this research field.

Register HERE to attend the seminar via Zoom.

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CoNVaT, the ‘Nanotrap’ for the coronavirus – highlighted by BBVA Fundation

Prof. Laura M. Lechuga, Scientific Director of NANBIOSIS Unit 4 Biodeposition and Biodetection Unit (from CIBER-BBN and ICN2-CSCIC) was awarded with the Physics, Innovation and Technology Award of the Royal Spanish Physics Society (RSEF) and the BBVA Foundation 2016.

BBVA Foundation has dedicated an article to explain the EU CoNVaT project, led by Laura Lechuga, whose objective is to obtain a diagnostic test for COVID-19 from the first day of infection, fast but highly sensitive, and which does not require a laboratory or qualified personnel. A test made with extremely sophisticated technology, and at the same time low cost, applicable to future waves of the epidemic. It is financed with more than two million euros by the European Union with a duration of one year.

The test is a biosensor that uses nanophotonics, and it will be used in two devices: one will detect virus proteins, the other, its genetic material. The heart of the device, and what gives it its main advantage over other existing diagnostic tests, is a chip that implements one of the most sensitive measurement techniques in physics: photonic interferometry. It is based on the idea that a beam of light undergoes small but measurable changes when it intersects an object. On the CoNVaT project chip, changes in the light beam will alert to the presence of the virus in the sample.

The test that will detect virus proteins is what is technically called an ‘antigen test’. It can be carried out in health centers or at sampling points, by non-specialized staff, and will give results in less than thirty minutes. Saliva samples will surely be used, although researchers are still studying it.

“The technique is so sensitive that it will be able to detect the presence of the virus from the first day of infection,” explains Lechuga. “And it will not only tell if the virus is or not, but also in what quantity. This is important because it gives an idea of how advanced the infection is. ”

‘Nanotrap’ for the coronavirus

The device will occupy what a shoe box, but at its core, where the measurement takes place, everything happens on a nanometric scale, that is, to dimensions of millionths of millimeters. It is, in essence, a nanotrap for proteins. Researchers attach proteins designed in the laboratory specifically to trap certain proteins in the virus envelope to the chip; both fit as a key and lock, so that the proteins fixed on the chip are actually hooks of the highest specificity – they only capture the virus’s proteins.

Channels a few nanometers thick have also been engraved on the chip: light passes through them. These guides form a circuit with a single input, but which forks, so that only one of the branches passes through the protein trap. When both light beams meet again, it is observed that the one that has interacted with the proteins has undergone modifications, and it is the analysis of these changes that reveals the presence of the virus, and in what quantity.

The device to detect genetic material of the virus -RNA- is based on the same principle, but it should be done in the laboratory. Lettuce explains that its purpose will be above all to confirm the result of the first. It will be faster than the PCR currently used – less than half an hour versus several hours – and it does not need specialized technicians – something indispensable with PCR.

Biology is the most difficult

“In this type of device, the biological part is by far the most complex,” explains Lechuga. Anchor the proteins to the chip at the correct angle, stabilize them to resist movement, keep them in a liquid medium … “they are thirty steps”.

It is a very sophisticated technology but already validated in the clinic. The ICN2 Biosensors and Bioanalytical Applications Group led by Lechuga has developed, among others, nano-biosensors that detect colon cancer early in blood samples, and also for tuberculosis and sepsis cases. “One of the reasons we have achieved the ConVAT project is that we have experience with clinical samples, which is really a completely different world than the laboratory.”

The group advances fast. They started working about three weeks ago and have just received from their French collaborators proteins that match those of the virus. Patient validation, when the device is completed, will be handled by the group in Italy.

The objective, at the end of the project, is for a company to take care of scaling the technology to bring it to the market at an affordable price. “Especially in a situation like the current one, we work with the idea that our work can reach everyone, as soon as possible,” says Lechuga.

Further information in Spanish in the original article by MÓNICA G. SALOMONE BBVA Foundation

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NANBIOSIS Scientists discover a promising effective alternative to reduse relapse rates in Diffuse Large B-cell Lymphoma Cells

Researchers of NANBIOSIS-ICTS Units from CIBER-BBN: U1 Protein Production Platform (PPP) at IBB-UAB, led by Antoni Villaverde and Unit 18 Nanotoxicology Unit at IBB-Hospital Sant Pau, led by Ramón Mangues, have demonstrated a potent T22-PE24-H6 antineoplastic effect, especially in blocking dissemination in a CXCR4⁺ DLBCL model without associated toxicity. Thereby, T22-PE24-H6 promises to become an effective alternative to treat CXCR4⁺ disseminated refractory or relapsed DLBCL patients.

Diffuse large B-cell lymphoma (DLBCL) is a cancer of B cells, a type of lymphocyte that is responsible for producing antibodies. It is the most common form of non-Hodgkin lymphoma among adults, with an annual incidence of 7–8 cases per 100,000 people per year in the US and UK.

One of the major problems in the therapeutic strategies is the relapse rates. CXCR4-overexpressing cancer cells are good targets for therapy because of their association with dissemination and relapse in R-CHOP treated DLBCL patients but show a narrow therapeutic index due to their systemic toxicity wich generate the induction of severe side effects. NANBIOSIS researchers have developed a therapeutic nanostructured protein T22-PE24-H6 that incorporates exotoxin A from Pseudomonas aeruginosa, which selectively targets lymphoma cells because of its specific interaction with a highly overexpressed CXCR4 receptor (CXCR4⁺) in DLBCL, demonstrating a potent T22-PE24-H6 antineoplastic effect, without associated toxicity. Thereby, T22-PE24-H6 promises to become an effective alternative to treat CXCR4⁺ disseminated refractory or relapsed DLBCL patients

The bioluminescent follow-up of cancer cells and toxicity studies has been performed in the ICTS Nanbiosis Platform, using its CIBER-BBN Nanotoxicology Unit and Protein production has been performed by the ICTS “NANBIOSIS”, more specifically by the Protein Production Platform of CIBER-BBN/ IBB

Article of reference:

Falgàs A, Pallarès V, Serna N, Sánchez-García L, Sierra J, Gallardo A, Alba-Castellón L, Álamo P, Unzueta U, Villaverde A, Vázquez E, Mangues R, Casanova I. Selective delivery of T22-PE24-H6 to CXCR4⁺ diffuse large B-cell lymphoma cells leads to wide therapeutic index in a disseminated mouse model. Theranostics 2020; 10(12):5169-5180. doi:10.7150/thno.43231. Available from http://www.thno.org/v10p5169.htm

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Neurocardiac Oscillation in Repolarization and Cardiac Arrhythmias

David Sampedro and Esther Pueyo, from NANBIOSIS Unit 27 High Performance Computing (CIBER-BBN, I3A-UZ) have conducted a research about Neurocardiac Oscillation in Repolarization and Cardiac Arrhythmias.

Recent studies in humans and dogs have shown that ventricular repolarization exhibits a low-frequency (LF) oscillatory pattern following enhanced sympathetic activity, which has been related to arrhythmic risk. The appearance of LF oscillations in ventricular repolarization is, however, not immediate, but it may take up to some minutes.

This study seeks to characterize the time course of the action potential (AP) duration (APD) oscillatory behavior in response to sympathetic provocations, unveil its underlying mechanisms and establish a potential link to arrhythmogenesis under disease conditions

The conclussion was that the time course of LF oscillatory behavior of APD in response to increased sympathetic activity presents high inter-individual variability, which is associated with different expression and PKA phosph

Computations were performed by ICTS NANBIOSIS

Article of reference:

David Adolfo Sampedro-Puente^,Jesus Fernandez-Bes, Norbert Szentandrássy, Péter Nánási, Esther Pueyo. Time Course of Low-Frequency Oscillatory Behavior in Human Ventricular repolarization Following Enhanced Sympathetic Activity and Relation to Arrhythmogenesis” published in the scientifiec journal. Front. Physiol., 14 January 2020 | https://doi.org/10.3389/fphys.2019.01547

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Prof. Laura Lechuga is part of the experts advising the government on the COVID-19 crisis

The Fourth Vice-President of the Government and Minister for the Ecological Transition and the Demographic Challenge, Teresa Ribera, and the Minister of Science and Innovation, Pedro Duque, met with the Multidisciplinary Working Group that advises and supports the Ministry of Science and Innovation in scientific matters related to the COVID-19 and its future consequences. It also coordinates the preparation of reports and will propose the necessary modifications to improve the response to similar crises in the future.

The group is formed by 16 experts in fields such as law, economy, biochemistry, bioinformatics, artificial intelligence, physics, statistics, immunology or medicine. Prof. Laura Lechuga, Scientific Director of @Nanbiosis U4 Biodeposition and Biodetection Unit, from CIBER-BBN and ICN2, is one of the experts of this group, providing advice from the nanotechnology area, particularly in the field of nanobiosensors and bioanalytical applications.

More information in Science and Innovation Ministry portal web

Source: ICN2

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JUMISC will carry out PCR test for COVID-19 infections

The Institute of Health Carlos III (ISCIII), depending of the the Ministry of Science and Innovation, has validated thirty new centers for carrying out PCR tests for COVID-19 infections throughout Spain. The Minimally Invasive Surgery Center, together with the University of Extremadura (JUMISC), partner of NANBIOSIS, will carry out these PCR tests in the laboratory of the veterinary faculty of Cáceres, as it is a P2 biosafety laboratory that is already approved.

They will have the capacity to perform 200 daily PCRs and will work with the samples that the the Extremadura Health Service will send them.

In total, Spain has 54 laboratories to practice the tests that determine COVID-19 infections.

Laboratories validated to carry out these PCR tests have to meet a series of requirements: have personnel trained in molecular biology techniques; have the capacity to work with level 2 infectious samples, biosafety cabinet and adequate equipment; have the capacity to produce inactivation reagents, and manage extraction techniques by their own means that do not subtract capacities from hospital centers, among others

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Nanbiosis

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