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News U25

Philipps-Universität Marburg (Germany) -NANBIOSIS U25 collaboration on the study of tumour microenvironment (TME) changes in Glioblastoma

The scientific coordinator of NANBIOSIS U25 “RNM: Biomedical Application I”, Ana Paula Candiota, was recently awarded with a mobility fellowship from CIBER-BBN for a scientific exchange visit to Philipps-Universität Marburg, in Marburg, Germany.


This scientific stage was motivated for a sustained collaboration between the research groups (GABRMN, in charge of U25 and Neurosurgery Lab group in Marburg), regarding the study of tumour microenvironment (TME) changes in Glioblastoma and possible relationship with the noninvasive MRSI-based biomarkers. Both groups have applied together to different funding calls including ERA-NET Transcan and Pathfinder Open, and Marburg group has hosted a predoctoral stage from a GABRMN PhD student.

The University of Marburg is the university with the longest tradition in Hesse, founded in 1527. With thirteen Leibniz Prize winners, the University of Marburg is one of the leading research institutions in the State of Hesse. Related to the Medicine Faculty of the Philipps University of Marburg is the Uniklinikum Giessend Und Marburg (UKGM), in which the Neurosurgery Lab, lead by Prof. Jörg-Walter Bartsch, is located. This group is hosting Dr. Candiota stage until September 9th.

The main objectives of this short stage are to strength the scientific collaboration, to finish pending work related to TME GL261 glioblastoma, to get familiarized with some approaches used in Marburg and not mastered by GABRMN, and finally to give a talk to group and clinical members, highlighting the potential of U25 and the translational characteristics of the common projects held by both institutions.

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Two NANBIOSIS Units of CIBER-BBN at UAB, one of the 300 best universities in the world, according the Shanghai Ranking

The Academic Ranking of World Universities (ARWU), known as Shanghai Ranking, which was made public on August 15, places the Autonomous University of Barcelona among the elite of the 300 best universities in the world.

This indicator organizes up to 20,000 university centers worldwide,
based on transparent methodology and objective third-party data. ARWU is regarded as one of the three most influential and widely observed university rankings

Two of NANBIOSIS Units created by UAB and CIBER-BBN are part of this university:

U1 Protein Production Platform (PPP), led by Toni Villaverde, Neus Ferrer and Mercedes Marquez, offer an “tailored” service for the design, production and purification of recombinant proteins using both prokaryotic and eukaryotic expression systems

U25 NMR: Biomedical Applications I, led by Carles Arús and Ana Paula Candiota, with a recognized research track record in the use of NMR as a tool for biomedical applications, and more especifically to identify biomarkers of different pathologies, the main objective of this unit is the acquisition, processing and/or interpretation of Nuclear Magnetic Resonance data

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Metal-free contrast agents: novel approaches

The joint expertise of CIBER-BBN Nanomol Group – NANBIOSIS U6 from at ICMAB-CSIC (José Vidal and Vega Lloveras) and NANBIOSIS U25 at UAB (Ana Paula Candiota), led to a recently published article in the prestigious journal Biomacromolecules

Brain tumours such as Glioblastomas are a challenge in the clinics and proper diagnosis and follow-up are crucial for patient outcome. Contrast agents are usually administered to patients for assessing blood brain barrier integrity and quantitation of enhancing areas are part of the clinical criteria for estimating response/relapse. However, most contrast agents currently used in clinics are based in metal elements such as Gadolinium and are not exempt of risks. In addition, due to the renal excretion route, administering such agents to some patients is contraindicated. Our work explored the potential of organic radicals anchored to dendrimers to act as contrast agents for glioblastoma studies, proposing a metal-free alternative for contrast enhanced glioblastoma studies. The article describes details of synthesis and characterization of these agents, as well as in vivo, ex vivo and in vivo magnetic resonance studies. The orthotopic immunocompetent GL261 glioblastoma murine model was used for in vivo and ex vivo studies. The novel contrast agent proved to be non-harmful for wild type mice and produced sustained and long lasting contrast in tumour-bearing mice, even in much lower doses in comparison with gadolinium administration.

The diagnosis and follow-up of high-grade brain tumours such as glioblastomas relies mostly in MRI, and contrast agents currently used are based on Gadolinium, which is not exempt of risks. The resarchers’ approach explores organic radicals anchored to dendrimers as a metal-free alternative to produce contrast enhancement in MRI, safer than Gadolinium-based compounds, and with translational potential.

Article of reference:
Zhang S, Lloveras V, Lope-Piedrafita S, Calero-Pérez P, Wu S, Candiota AP, Vidal-Gancedo J. Metal-Free Radical Dendrimers as MRI Contrast Agents fof Glioblastoma Diagnosis: Ex Vivo and In Vivo Approaches. Biomacromolecules. 2022 Jun 24. doi: 10.1021/acs.biomac.2c00088.

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Improving quality of MR spectra from mouse brain. MRSI-detected pattern in glioblastoma patients

Work performed at Unit 25 of Nanbiosis ICTS of “NMR: Biomedical ApplicationsI” is being shown at the Joint annual meeting ISMRM-ESMRMB (May 7-12th) London, with the participation of CIBER-BBN group members Ana Paula Candiota, Silvia Lope-Piedrafita, Miquel Cabañas (abstract 1), Carles Arús, Gulnur Ungan, Margarida Julià-Sapé, Alfredo Vellido and Carles Majós (abstract 2).

In the first abstract, entitled “High resolution Multi-voxel spectroscopy using CSI-semi-LASER for mouse brain preclinical studies” we focused into improving quality of MR spectra obtained from mouse brain, a key factor when trying to pursue metabolomic-based biomarkers.

The second abstract, entitled “MRSI-detected pattern in glioblastoma patients one month after concomitant chemoradiotherapy” presented a study with a retrospective MRSI set of 31 glioblastoma patients and investigation of spectral patterns predictive of true progression or pseudoprogression.

The International Society for Magnetic Resonance in Medicine (ISMRM) and The European Society for Magnetic Resonance in Medicine and Biology (ESMRMB) are prestigious scientific societies devoted to magnetic resonance-based studies at international and European levels with participation of the most renowned scientifics in the field. This year, the international and european events are joined into a single event (https://www.ismrm.org/22m/)

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Targeting of the breast cancer stem cells to improve the treatment of triple negative breast cancer

On April 1st PhD candidate Patricia Cámara Sánchez defended her doctoral thesis entitled “Targeting of the breast cancer stem cells to improve the treatment of triple negative breast cancer“, where ICTS-Nanbiosis Unit 20 participated in the in vivo assays. The thesis was supervised by Dr. Ibane Abasolo  (scientific director of Unit 20 from CIBER-BBN and VHIR). Nanbiosis was also present within the jury, with Dr. Ana Paula Candiota (scientific coordinator of Unit 25 from CIBER-BBN and UAB) acting as secretary.

Patricia Cámara graduated as biochemist, did the master’s degree in Translational Biomedical Research from VHIR-UAB. Shortly after, started the PhD, which was aimed at improving the treatment of very deadly subtype of breast cancer by using different nanoformulations to specifically target the cancer stem cells. The now doctor Cámara-Sánchez screened up to 20 small drugs with anti-cancer stem cell activity, found synergistic ratios with conventional chemotherapeutic agents, and finally developed polymeric micelles encapsulating selected drugs. During the discussion of the dissertation, the need of additional in vivo assays was highlighted, as well as the potential use of MR provided by the U25, to explore non-invasively the metabolomic differences between cancer stem cells and regular cancer cells.

‘I’m very grateful for the opportunity to have been part of this amazing project. It has been a very enriching experience’, she explains. ‘After 5 years of research, I finish the PhD feeling very proud of having contributed to the fight against this aggressive subtype of breast cancer’, she adds. From now on, new research lines will bring forward the synergies between both units of NANBIOSIS, reinforcing a collaboration started several years ago and reflected in joint papers.

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Radical Dendrimers as Contrast Agents for Magnetic Resonance Imaging

José Vidal Gancedo, researcher from ICMAB-CSIC and CIBER-BBN is leading the project VIRADEN: “In vivo Studies of Radical Dendrimers as Contrast Agents for Magnetic Resonance Imaging“, one of the ICMAB Frontier Interdisciplinary Projects (FIP) 2021.

The project aims to evaluate the new contrast agents for MRI based on organic radical dendrimers developed in his group, to substitute the currently used contrast agents based on toxic metals, with the final goal of obtaining useful contrast agents in the early detection of tumors

José Vidal has explained NANBIOSIS participation in the project through Biomaterial Processing and Nanostructuring equipments of NANBIOSIS U6 counting with the expertise of José Amable Bernabé and the Ex vivo and in vivo studies with dendrimers for MRI of NANBIOSIS U25 with the expertise of Ana Paula Candiota.

ICMAB FIPs are possible thanks to the financial support from the Spanish Ministry Science and Innovation, through the “Severo Ochoa” Programme for Centres of Excellence in R&D (CEX2019-000917-S).

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Novel nano-encapsulation approach for efficient dopamine delivery in Parkinson’s treatment

UAB

Parkinson’s disease (PD) is a common neurodegenerative disorder caused by the death of dopaminergic neurons in a part of the brain (known as substantia nigra pars compacta), which leads to a deficit of dopamine (DA), one of the main neurotransmitters active in the central nervous system. Symptomatic treatment focuses on increasing the concentration of dopamine into the brain.

However, dopamine is not directly administered, because it is unable to cross the so called blood-brain barrier, which prevents some of the substances circulating in the blood to penetrate into the nervous system. Thus, DA precursor levodopa (L-DOPA) –an amino-acid which participates in the synthesis of dopamine– is used, due to its better ability to cross such barrier. Nevertheless, long-term and intermittent administration of this drug is associated with important disabling complications, such as motor disorders and involuntary muscle movements.

In a paper recently published in ACS Nano, synthetic melanin-like nanoparticles are used to overcome these limitations. This research was coordinated by Dr Daniel Ruiz-Molina, leader of the ICN2 Nanostructured Functional Materials Group, and Dr Julia Lorenzo, leader of the Protein Engineering Group at the Institute of Biotehcnology and Biomedicine (IBB) of the Universitat Autònoma de Barcelona (UAB), and was developed in collaboration with the Neurodegenerative Diseases group of Vall d’Hebron Research Institute (VHIR), led by Prof. Miquel Vila.

The main objective of this work was to obtain a “nanoplatform” –which is a biocompatible nano-structure including the substance to be delivered– able to reach the brain through a noninvasive route and generate a slow and controlled release of dopamine. A tailor-made nanoscale coordination polymer (NCP), characterized by the reversible incorporation of DA as its principal component, was tested in vitro and in vivo in rats. Intranasal administration of these nanoparticles, called DA-NCPs, showed a relevant biocompatibility, non-toxicity and a fast and efficient distribution of dopamine in the central nervous system of the animals (avoiding the blood-brain barrier).

Ex vivo and in vivo preclinical MRI acquisitions were performed at U25 of NANBIOSIS ICTS NMR: Biomedical Applications I

As reported by the researchers, the proposed method is effective in delivering dopamine to the brain and, thus, in reversing Parkinson’s symptoms. In addition, the synthetic methodology used is simple, cheap and exhibited a satisfactory yield (with a DA loading efficiency up to 60%).

These findings establish nanoscale coordination polymers as promising future candidates for efficient nasal delivery of drugs to the central nervous system, and thus for the symptomatic treatment of people affected by Parkinson’s and other neurodegenerative disorders. This type of nano-formulation and administration route may also pave the way to the development of other platforms able to deliver a wide range of drugs into the brain in a controlled manner, for the treatment of various brain diseases (such as brain tumours, Alzheimer’s, Epilepsy).

Reference article:

Javier García-Pardo, Fernando Novio, Fabiana Nador, Ivana Cavaliere, Salvio Suárez-García, Silvia Lope-Piedrafita, Ana Paula Candiota, Jordi Romero-Gimenez, Beatriz Rodríguez-Galván, Jordi Bové, Miquel Vila, Julia Lorenzo, and Daniel Ruiz-Molina, Bioinspired Theranostic Coordination Polymer Nanoparticles for Intranasal Dopamine Replacement in Parkinson’s Disease. ACS Nano 2021, 15, 5, 8592–8609, May 2021. [DOI]

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Participation of NANBIOSIS U25 in the Valorisation Project MR-INITIATE

The Unit 25 of the ICTS NANBIOSIS will be enrolled, through its scientific coordinator Ana Paula Candiota, in a research valorisation project recently granted by CIBER: “Noninvasive MR-based ImagiNg of Immune sysTem action during glIoblastomA TreatmEnt (MR-INITIATE)”

Such project has the aim to increase the TRL of therapy response follow-up methods in glioblastomas, using technological approaches performed at  U25 of NANBIOSIS NMR: Biomedical Applications I

The project will be financed with € 20,000.

The CIBER-BBN transfer program

The CIBER-BBN transfer program through its call for transfer and valorization projects has been designed to promote the transfer to the industrial sector of scientific or technological results derived from the research carried out by the CIBER-BBN groups. These transfer projects will make it possible to support the commercialization of said results, since there is a company that has shown interest in them and that provides at least, the same financing than CIBER-BBN for their achievement.

The call for valorization projects is in its fourth edition, having already financed a total of fourteen projects.

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NANBIOSIS Scientific Women in the International Day of Women and Girls in Science

Today February 11 is the International Day of Women and Girls in Science, a day to raise awareness of the gender gap in science and technology.

According to the United Nations, while yet women and girls continue to be excluded from participating fully in science, science and gender equality are vital to achieve the internationally agreed development goals, including the 2030 Agenda for Sustainable Development. Thus, in recent years, the international community has made a great effort to inspire and promote the participation of women and girls in science.

NANBIOSIS wants to acknowledge  the efforts made by scientific women who struggle every day to contribute their bit to Science and highlight their essential role in nowadays research. Especially we want to recognize the work of scientists women involved in NANBIOSIS, whatever is the nature of their contribution: technical, scientific development, management, coordination, direction, etc; just to mention some examples:
Neus Ferrer and Mercedes Márquez in the Scientific Direction and Coordination of Unit 1 Protein Production Platform (PPP)
Pilar Marco and Nuria Pascual in the Management and Scientific Coordination of U2 Custom Antibody Service (CAbS) 
Miriam Royo in the Scientific Direction of U3 Synthesis of Peptides Unit
Nora Ventosa and Nathaly Segovia in the Scientific Direction and Technical Coordination of U6 Biomaterial Processing and Nanostructuring Unit
Isabel Oliveira and Teresa Galán in the Coordination of U7 Nanotecnology Unit
Rosa Villa and Gemma Gabriel in the Management and Scientific Coordination of U8 Micro – Nano Technology Unit
Gema Martínez in the Scientific Coordination of U9 Synthesis of Nanoparticles Unit
Fany Peña in the Scientific Coordination of U13 Tissue & Scaffold Characterization Unit
Mª Luisa González Martín and Margarita Hierro in the of Direction and Scientific Coordination of U16 Tissue & Scaffold Characterization Unit
Gemma Pascual and Isabel Trabado in the Coordination of the U17 Confocal Microscopy Service
Isolda Casanova in the Scientific Coordination of U18 Nanotoxicology Unit
Beatriz Moreno in the Scientific Direction of Unit 19 Clinical tests lab
Ibane Abásolo in the Scientific Coordination of Unit 20 In Vivo Experimental Platformt
Verónica Crisóstomo in the Scientific Direction of Unit 24 Medical Imaging 
Ana Paula Candiota in the Scientific Coordination of Unit 25 Biomedical Applications I 
Maria Luisa García in the Scientific Direction of U28 NanoImaging Unit from Bionand, recently incorporated to NANBIOSIS, Anna Aviñó in the Scientific Coordination of U29 Oligonucleotide Synthesis Platform (OSP) – and

Nerea Argarate in the coordination of NANBIOSIS

Thanks to all of you and your teams!

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12th Workshop on Magnetic Resonance Spectroscopy and Imaging (MRI/MRS) Applied to Laboratory Animals

We are glad to inform that registration is now open for the 12th Workshop on Magnetic Resonance Spectroscopy and Imaging (MRI/MRS) Applied to Laboratory Animals, organized by the Biochemistry and Molecular Biology Department (UAB) and the Nuclear Magnetic Resonance Facility, which is also part of the NANBIOSIS ICTS U25 NMR: Biomedical Applications I. Workshop will take place February 15-18th, 2021.
This course combines a comprehensive series of lectures on the technology of Magnetic resonance spectroscopy and imaging (MRS/MRI) with hands-on laboratory sessions to provide practical demonstrations of key concepts and procedures for preclinical studies.
Whether you are considering MRI as a research tool in your lab or just would like to learn more about MRI, this workshop addresses practical aspects of experimental MRI with laboratory animals and provide valuable hands-on experience on a 7 Tesla Bruker BioSpec spectrometer.

Online registration:
(http://sermn.uab.cat/wiki/doku.php?id=formulari_curs_mri_mrs)

For more detailed information, please go to:
http://sermn.uab.cat/2021/01/12th-workshop-mrs-mri-small-animals/

Please note that a limited number of attendants is currently allowed (maximum 4). Anticipated reservation is strongly recommended.

See the workshop brochure 

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