News

“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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A new compound removes senescent cells and reduces toxicity in cancer treatment

Scientists of NANBIOSIS unit 26 NMR: Biomedical Applications II, (of CIBER-BBN and the Universitat Politècnica de València), together with researchers from the Principe Felipe Research Center and the University of Cambridge confirm the therapeutic potential of using a new conjugated drug, Nav-Gal, in combination with chemotherapy

Nav-Gal selectively removes tumourigenic senescent cells without attacking healthy cells and reduces the toxicity of platelets

The accumulation of senescent cells plays a significant role in cancer pathogenesis and other diseases. However, senolytic drugs (intended to remove senescent cells) present significant toxicity, which limits their therapeutic benefits.

Now, a new international study involving researchers at CIBER-BBN, the Universitat Politècnica de València (UPV) and the Principe Felipe Research Center, in collaboration with the University of Cambridge, have just proved the efficiency of a new conjugated drug, Nav-Gal, which selectively removes senescent cells, minimising the effect on healthy cells and reducing toxicity through this therapy. The use of this drug in combination with chemotherapy could be confirmed as a promising strategy in treating cancer. The auspicious results of this study have been published in the journal Aging Cell.

Senescent cells: the target

Senescence is a response to cell damage and stress characterised by the arrest of the cell cycle. When aging, cells permanently stop dividing, thus preventing the propagation of damaged and dysfunctional cells. However, eventually, a massive quantity of senescent cells accumulate in tissues, resulting in the onset and progression of multiple disorders, including diabetes, cardiovascular diseases, lung fibrosis, neurological disorders or cancer. Moreover, in the case of cancer, several chemotherapies result in cell senescence, and this accumulation of senescent cells due to the treatments has been related to tumourigenesis, associated with metastasis and the recurrence of tumours in different types of cancer. That is why the search for new drugs that remove senescent cells induced by cancer treatments is a key question in order to guarantee the total eradication of the tumour and prevent them from recurring.

On this front, senolytic drugs (compounds that kill senescent cells using several mechanisms) are a promising therapeutic alternative in oncology and for treating other diseases related to the accumulation of senescent cells. However, today senolytics present a low specificity because they also damage healthy cells, and have significant toxicities, which reduce their therapeutic benefits.

Reducing toxicity and preventing “collateral damages”

In this new study, published in Aging Cell, researchers at CIBER-BBN, the Universitat Politècnica de València (UPV) and the Principe Felipe Research Center, in collaboration with researchers from CRUK, at the University of Cambridge, worked on the design of a second-generation senolytic, which is more specific and less toxic. They focused on Navitoclax, a drug validated in preclinical models that proved to have a high capacity to destroy senescent cells, modifying it with acetylated-galactose.

The new compound, called Nav-Gal, results in a drug with selective, wide-ranging senolytic activity, which induces the death of senescent cells while preserving the activity of healthy cells.

“To summarize, we suggest the galactose conjugation with certain drugs as a versatile methodology to develop second-generation prodrugs with high senolytic activity and reduced toxicity,” explains Ramón Martínez Máñez, member of the Interuniversity Research Institute for Molecular Recognition and Technological Development (IDM) of the Universitat Politècnica de València, Scientific Director of CIBER-BBN and one of the study’s coordinators.

The researchers tested this drug in combination with chemotherapy (cisplatin) in human lung cancer cells, proving that treatment with cisplatin and Nav-Gal results in the eradication of senescent lung cancer cells and significantly reducing tumour growth. “This study provides evidence of the potential clinical application of combining senescence-induction chemotherapies with senotherapies in cancer,” explains Daniel Muñoz Espín from the CRUK Early Detection Programme of the University of Cambridge. Moreover, the compound Nav-Gal reduced platelet toxicity and the thrombopenia (reduction of the platelet circulation in bloodstream) caused by the previous drug, Navitoclax.

Reference article:

Galacto‐conjugation of Navitoclax as an efficient strategy to increase senolytic specificity and reduce platelet toxicity

https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13142

About CIBER-BBN

CIBER (Consorcio Centro de Investigación Biomédica en Red, M.P.) belongs to the Institute of Health Carlos III of the Spanish Ministry of Science and Innovation, and it is also funded by the European Regional Development Fund (ERDF). The CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) is made up of 46 research groups, selected for their renowned international scientific prestige, that mainly work within three scientific programmes: Bioengineering and Biomedical Imaging, Biomaterials and Tissue Engineering, and Nanomedicine. Its research work is oriented toward the development of prevention, diagnosis and monitoring systems as well as technologies for specific therapies such as Regenerative Medicine and Nanotherapies.

Further information

CIBER Communication Department

comunicacion@ciberisciii.es / 91 171 8119

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Pilar Marco explains on TV her group’s research against Covid-19 pandemic

M.-Pilar Marco, Scientific Director of NANBIOSIS Unit 2 Custom Antibody Service (CAbS) has been interviewed on Spanish TV (RTVE) to talk about her research against the Covid-19 pandemic in the frame of the CSIC POC4CoV project, for the development of new and rapid diagnostic tools.

Nb4D group of CIBER-BBN and IQAC-CSIC, led by Prof. Marco is working on the development of tests to increase the efficiency and speed of diagnosis of the methods currently on the market.

According to Pilar Marco, the new strategy of the project differs basically in two fundamental aspects: on the one hand the technology, which is based on the current knowledge of some of the CSIC’s research groups in micro and nano techno technology and, on the other hand, in the selection strategy of the antigens that will produce a more specific and sensitive response to the or SARS-COV-2.

The time required to develop these tests is relatively short since researchers have the advantage of having detection technologies already developed and tested in other types of projects, but even so, these tests need between 6 and 8 months of development to obtain the first prototypes that, obviously, will have to be validated so that they can be made available in the market in a safely. Therefore the new tests will help us to be much better prepared before the new waves of the pandemic expected by the epidemiologists.

The interview can be watched in the following link (0:41:50)

Further information on POC4CoV project here

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Scientists from NANBIOSIS selected by Barcelona Activa “Preacceleration” Program

Nora Ventosa and Nathaly Segovia, (Scientific Director and Coordinator of NANBIOSIS U6 Biomaterial Processing and Nanostructuring Unit from CIBER-BBN and ICMAB_CSIC), have been selected as part of the NARTIC Project team for an incubation program by Barcelona Activa. NARTIC is a biotech project for the development of molecular therapy based on Quatsomes for diseases such as cancer.

The NARTIC project has recently been selected for the 6th edition of the Preacceleration Program, an incubation program developed by Barcelona Activa for starting ventures with a high technological impact.

The project team includes two researchers from the Molecular Nanoscience and Organic Materials (NANOMOL) group (from CIBER-BBN and ICMAB-CSIC): Nora Ventosa, as scientific advisor, and Nathaly Segovia, as scientific consultant for technology transfer. The rest of the team is formed by Ariadna Boloix, PhD fellow between the ICMAB and the Vall d’Hebron Research Institute (VHIR), as entrepreneur, Miquel Segura, researcher at VHIR, as scientific advisor, and Martí Archs, Innovation & Tech Transfer Project Manager at VHIR, as innovation and tech transfer consultant.

The project has already developed a laboratory scale proof of concept for their nanomedicine, which uses RNA molecules conjugated to Quatsomes to design a biocompatible lipidic nanoparticle that transports RNA molecules, like microRNAs or siRNAs, and releases them within cancerous cells to induce an anti-tumoral activity. This has been achieved through collaboration between the Recerca Translacional del Càncer Infantil i de l’Adolescència group at the Vall d’Hebron Research Institute (VHIR) and the NANOMOL team at ICMAB.

This program will allow to further define the business model for the project, as well as kickstart their access to the market, through workshops with experts in the field, covering topics like product discovery, lean start ups, and intelectual property, amongst others. They will also get access to the MediaTIC incubator and the possibility of a 5.000€ prize at the end of the process.

For further information: here

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Microencapsulated Insulin-Like Growth Factor-1 therapy improves cardiac function and reduces fibrosis in a porcine acute myocardial infarction model

Researchers of NANBIOSIS Units at JUMISC. led by Verónica Crisóstomo, Scientific Director of NANBIOSIS unit 24 of Medical Imaging, have just published an article in the Journal Scientific Report

Cardiovascular diseases, especially ischemic heart disease, are the leading cause of mortality worldwide. Conventional treatments have contributed to reduce early mortality after an acute myocardial infarction, but do not recover the damaged myocardial tissue. In the last two decades stem cell therapy has been studied for that purpose. Nowadays it is known now that stem cells are able to secrete combinations of biomolecules that modulate the composition of the damaged cardiac environment contributing to functional tissue repair by stimulating the migration, proliferation and survival of endogenous cardiac progenitor cells as well as attenuating fibrosis and modulating inflammation. Among the secreted substances, there are different cytokines, extracellular vesicles and growth factors including insulin-like growth factor-1 (IGF-1). Our researchers’ goal in this work has been to assess the safety and effectiveness of an intracoronary infusion of microencapsulated IGF-1 after acute myocardial infarction in a clinically relevant swine model of reperfused myocardial infarction.

Large animal studies have been conducted by the ICTS “NANBIOSIS”, more specifically by Units 14, 21, 22 and 24 of the Jesús Usón Minimally Invasive Surgery Centre.

Article:

Báez-Díaz, C., Blanco-Blázquez, V., Sánchez-Margallo, F. et al. Microencapsulated Insulin-Like Growth Factor-1 therapy improves cardiac function and reduces fibrosis in a porcine acute myocardial infarction model. Sci Rep 10, 7166 (2020).

https://doi.org/10.1038/s41598-020-64097-y

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