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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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A Concise Review on Nano-emulsion Formation by the Phase Inversion Composition (PIC) Method

Researchers of NANBIOSIS U12. Nanostructured liquid characterization unit from CIBER-BBN and IQAC-CSIC have recently published an interesting review entitled “A Concise Review on Nano-emulsion Formation by the Phase Inversion Composition (PIC) Method” in the JOURNAL OF SURFACTANTS AND DETERGENTS. https://doi.org/10.1002/jsde.12414

Studies of phase behavior and particle sizing were performed at the Nanostructured Liquid Characterization Unit, member of the NANBIOSIS ICTS.

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NANBIOSIS U27 researchers working in an App for the early diagnosis of covid-19 through mobile phones

Bsicos group researchers, from the I3A (Engineering Research Institute) of the University of Zaragoza and CIBER-BBN), Dr. Jesús Lázaro, Dr. Eduardo Gil, Dr. Raquel Bailón and Dr. Pablo Laguna, are working on a line of work for the search of solutions for the early diagnosis of Covid-19 cases, through the development of an App for mobile phones.

For almost three years, Dr. Jesús Lázaro, under the supervision of Professor Pablo Laguna, from the resarch group Bsicos, which coordinate Nanbiosis U27 High Performance Computing , have been working on the European project WECARMON (Wearable Cardiorespiratory Monitor) for the development of an ambulatory system that would allow monitoring the cardiac and respiratory rhythm of patients with Clinical Obstructive Pulmonary Disease (COPD) and thus control and predict episodes of worsening of the disease.

However, the current situation of pandemic due to the SARS-CoV-2 coronavirus has led the researchers, with the approval of the European Commission, to temporarily redirect their objective, foccusing their work in search of solutions for the early diagnosis of the covid-19.
 
The work carried out for patients with a respiratory disease such as COPD could now serve for the early detection of people with symptoms of covid-19, before even having fever, but also for asymptomatic people, since the rapid variation of these parameters is known. in the initial stages of other respiratory conditions. Our researchers will use these cardiac and respiratory parameters, indirect markers of the autonomic nervous system and, therefore, sensitive to the response of the immune system, potentially helping to identify possible cases of covid-19 earlier. A technological tool that could join the fight to control this pandemic.

Jesús Lázaro has recently made a two-year stay at Connecticut University in the United States, partner of the WECARMON project in which he was working with Pablo Laguna. Two other researchers from the Bsicos group, Dr. Raquel Bailón and Dr. Eduardo Gil, have also decided to redirect their lines of research and focus on the SARS-CoV-2 coronavirus. Re-directing research lines with different objectives to join the fight against the coronavirus is a great challenge and shows the relenvance of cutting-edge research to provide answers to the arising challenges in our society.
 
Jesús Lázaro explains that the application they are working on would allow a pre-selection of people at risk by analysing markers of the autonomic nervous system that would be measured on a mobile phone. ” At this moment, the above-mentioned four researchers have already developed the algorithms for other platforms and they are working now on an App using the technology of the cameras and the flashlight of the mobiles. A sudden change in heart rate variability or an increase in respiratory rate could give a sensitive and early warning, to resort to other more specific diagnostic tests for covid-19, decreasing the latency time, which has been sadly shown key in this pandemic. The developments and validation, those already made and those planned, are being carried out using NANBIOSIS U27 High Performance Computing (I3A-Unizar/ CIBER-BBN)

The WECARMON project is funded by the H2020 Research and Innovation Program of the European Commission. It is part of the Marie Sklodowska-Curie Individual Actions, whose objective is to promote the professional career of young and brilliant researchers, expanding their knowledge through training, stays abroad and internships, in order to help them develop all their potential as researchers.

Related news:

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Wearable Armband Device for Daily Life Electrocardiogram Monitoring

Researchers Dr. Jesús Lázaro and Dr. Pablo Laguna, from Bsicos group, which coordinate Nanbiosis U27 High Performance Computing from I3A -Engineering Research Institute of the University of Zaragoza- and CIBER-BBN, in the framework of the European project WECARMON (Wearable Cardiorespiratory Monitor) are coauthors of the recently published article titeled “Wearable Armband Device for Daily Life Electrocardiogram Monitoring” in the Scientific Journal IEEE Transactions on Biomedical Engineering ( Early Access )

“Our long-term wearable armband is evaluated as heart rate monitor with 24h recordings during daily life”, explained Dr. Jesús Lázaro.

A wearable armband electrocardiogram (ECG) monitor has been used for daily life monitoring. The armband records three ECG channels, one electromyogram (EMG) channel, and tri-axial accelerometer signals. Contrary to conventional Holter monitors, the armband-based ECG device is convenient for long-term daily life monitoring because it uses no obstructive leads and has dry electrodes (no hydrogels), which do not cause skin irritation even after a few days. Principal component analysis (PCA) and normalized least mean squares (NLMS) adaptive filtering were used to reduce the EMG noise from the ECG channels. An artifact detector and an optimal channel selector were developed based on a support vector machine (SVM) classifier with a radial basis function (RBF) kernel using features that are related to the ECG signal quality. Mean HR was estimated from the 24-hour armband recordings from 16 volunteers in segments of 10 seconds each. In addition, four classical HR variability (HRV) parameters (SDNN, RMSSD, and powers at low and high frequency bands) were computed. For comparison purposes, the same parameters were estimated also for data from a commercial Holter monitor. The armband provided usable data (difference less than 10% from Holter-estimated mean HR) during 75.25%/11.02% (inter-subject median/interquartile range) of segments when the user was not in bed, and during 98.49%/0.79% of the bed segments. The automatic artifact detector found 53.85%/17.09% of the data to be usable during the non-bed time, and 95.00%/2.35% to be usable during the time in bed. The HRV analysis obtained a relative error with respect to the Holter data not higher than 1.37% (inter-subject median/interquartile range). Although further studies have to be conducted for specific applications, results suggest that the armband device has a good potential for daily life HR monitoring, especially for applications such as arrhythmia or seizure detection, stress assessment, or sleep studies.

The developments are being carried out using NANBIOSIS U27 High Performance Computing (I3A-Unizar/ CIBER-BBN)

The WECARMON project is funded by the H2020 Research and Innovation Program of the European Commission. It is part of the Marie Sklodowska-Curie Individual Actions, whose objective is to promote the professional career of young and brilliant researchers, expanding their knowledge through training, stays abroad and internships, in order to help them develop all their potential as researchers.

Article of reference:

J. Lázaro, N. Reljin, M. B. Hossain, Y. Noh, P. Laguna and K. Chon, “Wearable Armband Device for Daily Life Electrocardiogram Monitoring,” in IEEE Transactions on Biomedical Engineering. 10.1109/TBME.2020.2987759

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Biosensors for Pandemics

Next 6 of May wii take place the On-line Conference Biosensors for Pandemics: Reliable and efficient nanotech-based diagnostics in emergency situations, will gather worldwide well known experts in biosensing technologies currently working in COVID-19 diagnostics or having very relevant technologies in the field.

Prof. Laura Lechuga, Scientific Director of NANBIOSIS U4 Biodeposition and Biodetection Unit of CIBER-BBN and ICN2-CSIC, will be one of the speakers. Laura Lechuga is coordinating the European proyect CONVAT: advanced nanobiosensing platforms for point-of-care diagnostics and surveillance of coronavirus for rapid diagnosis and monitoring of COVID ー 19, 

To join

Deadlines:

Abstract Submission (ePoster request): April 22, 2020

Author Submission Acceptance Notification: April 24, 2020

Flash Poster Acceptance Notification: April 24, 2020

Early Bird Registration Fee: April 24, 2020

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JUMISC will invest 7.3 million in the development of new surgical robots

The Jesús Usón Minimally Invasive Surgery Center (CCMIJU), partner of NANBIOSIS, has been granted the with the FID-CPI Innovative Public Procurement Program of the Ministry of Science and Innovation, as well as with the support of the Ministry of Economy, Science and Digital Agenda of the Board, for the development of the TREMIRS project “Minimally invasive robotic surgery systems” aimed at improve current techniques in laparoscopy and microsurgery

TREMIRS will improve current robotic surgical systems, providing better service to the patient, better ergonomics to the surgeon and greater benefits to the surgical team, achieving an increase in the quality of care. The project is endowed with 7,345,300 euros, and is co-financed 80 percent by the European Regional Development Fund-FEDER.

During the three-year duration of the project, a robotic platform for laparoscopic surgery will be developed that will facilitate new surgical approaches, improvements in the ergonomics of surgeons, advances in vision systems for the entire surgical team and the availability of new portable training tools. .

In the field of microsurgery, TREMIRS will develop a teleoperated robotic platform for reconstructive microsurgery, consisting of robotic microinstruments with high maneuverability and precision, the Board reports in a press release.

It will be used for soft tissue manipulation to perform microsurgical techniques such as anastomosis, suturing, and ligation of small anatomical structures such as blood vessels, nerves, and lymphatic ducts.

The development of both platforms will mean making new equipment available to the National Health System and the Extremadura Health System that is currently not available in the market and that will allow for the improvement of the quality of the services provided to the patient and improvements in surgical results.

Source: https://www.hoy.es/caceres/centro-cirugia-minima-20200419121007-nt.html#vca=fixed-btn&vso=rrss&vmc=tw&vli=C%C3%A1ceres

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U7-E14.

Microarrayer SPOTBOT2

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