2021 - Nanbiosis

CCMIJU leads an European Project based on mixed reality and 3D printing applied to medical education

The CCMIJU, partner of NANBIOSIS leads a European consortium of 9 partners from Spain, Norway, Netherlands, Romania and Greece to carry out the Research Project entitled “Mixed Reality in Medical Education Based on Interactive Applications“-MIREIA, funded by the Erasmus+ Programme – Key Action 2 (KA2): Cooperation for innovation and the exchange of good practices – Knowledge Alliances.

The consortium members will work together to develop an innovative methodology and tools to provide paedagogical content for customized training based on 3D models, such as anatomical models (with and without pathologies) built from real-patient cases (e.g. medical imaging studies) or virtual scenarios for basic training in minimally invasive surgery.

MIREIA will allow health professionals to train in virtual environments or physical simulators based on personalised 3D printed models. Mentors will also be able to create and share their clinical experience.

The Project leader Francisco Miguel Sánchez Margallo, Assistant Director of NANBIOSIS and Scientific Director of the CCMIJU, will be supported by a team of researchers and communication assistants led by Dr. Juan Alberto Sánchez Margallo, researcher in the Bioengineering and Health Technologies Department to carry out the research in cooperation with the rest of the consortium members.

Over a period of 3 years and with a budget of 1M€, the MIREIA Project aims to bridge the gap between classroom learning and laboratory training and actual clinical practice.

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A more effective nanomedicine has been developed for the treatment of Fabry rare disease.

28 February: International Rare Disease Day

This is one of the major achievements of the European Smart4Fabry project, which is now coming to an end after four years of work.
The results have been made possible by nanotechnology and the approach developed could be applied to other drugs in the future.
The new drug improves on current treatments and helps reduce costs and improve patients’ quality of life.

Barcelona, 26 February 2021.- The advance of nanomedicine opens up new possibilities in the development of drugs, such as the one recently developed for the rare disease Fabry, with improved efficacy compared to existing authorised treatments.

Thus, the European Smart4Fabry project has come to an end with one of the best results possible: the designation of a new orphan drug by the European Commission and the possibility of making progress in the treatment of Fabry, a rare disease that is estimated to affect approximately 2.6 out of every 10,000 people in the EU.

It is a chronic debilitating disease due to recurrent episodes of severe pain that is difficult to control with conventional analgesics, and it is life-threatening due to renal failure and associated cardiovascular and cerebrovascular complications.

“With this designation we have made a major achievement, not only for Fabry patients, but also for other pathologies that can benefit from this same approach, made possible by nanotechnology,” explained Nora Ventosa, Scientific Director of NANBIOSIS Unit 6 Biomaterial Processing and Nanostructuring Unit of CIBER-BBN and ICMAB-CSIC who coordinated the project.

Need for new treatments for the disease

This disease, also known as Anderson-Fabry disease, represents the most common lysosomal storage disorder. It is caused by an absence or deficiency of the enzyme α-galactosidase A (GLA), which results in the lysosomal accumulation of globotriaosylceramide (Gb3) and its derivatives in the lysosomes of a wide variety of tissues, responsible for the clinical manifestations. Current treatments consist of intravenous administration of the GLA enzyme, but have limited efficacy and poor biodistribution.

The drug that has been developed is a new nanoformulation of GLA (nanoGLA) that improves efficacy compared to the reference treatment with non-nanoformulated GLA. “The third-generation liposomal product we have developed in the project has demonstrated, at preclinical level, improved efficacy, compared to authorised enzyme replacement treatments, demonstrating that the strategy of supplying the affected cells with the GLA enzyme via the smart nanoliposome is highly successful”, explained Ibane Abasolo, Scientific Coordinator of NANBIOSIS U20 of CIBER-BBN and VHIR, who is responsible for the efficacy studies in the project.

The nanoGLA product was obtained using DELOS^TM formulation technology, an innovative platform for the robust production of nanomedicines in an efficient and sustainable manner.

The Committee for Orphan Medicinal Products, the European Medicines Agency’s (EMA) committee responsible for recommending orphan designation of medicines for rare diseases, has considered these results to have a clinically relevant advantage over current enzyme replacement therapies.

The designation of orphan drug, in addition to recognising the significant benefit of the new nanomedicine over products already licensed for Fabry disease, has important implications for the translation of the new therapeutic product from bench to bedside.

Those responsible for these results, including several CIBER-BBN groups, highlight that the new formulation helps to improve treatments, reduce costs, and improve the quality of life of Fabry patients.

Interdisciplinarity and public-private collaboration

The Smart4Fabry project has been running since 2017 thanks to European funding of €5.8 million, from the Horizon 2020 programme. This was possible thanks to the collaboration of several CIBER-BBN groups and NANBIOSIS Units at the Institute of Materials Science of Barcelona (ICMAB-CSIC) with the abouve mentioned NANBIOSIS Unit 6, the Institute for Advanced Chemistry of Catalonia (IQAC-CSIC) with NANBIOSIS Unit 3 of
Synthesis of Peptides Unit, led by Miriam Royo, the Vall d’Hebron Research Institute (VHIR) with NANBIOSIS Unit 20 and the Institute of Biotechnology and Biomedicine of the Autonomous University of Barcelona (IBB-UAB) with NANBIOSIS Unit 1 Protein Production Platform (PPP), whose work in this project was led by José Luis Corchero. It has also been necessary to contribute knowledge from different academic and business disciplines.

The project consortium also includes public institutions such as the University of Aarhus (Denmark), Technion Israel Institute of Technology (Israel) and Joanneum Research (Austria); and the companies Biokeralty (Spain); Nanomol Technologies SL (Spain); BioNanoNet (Austria), Drug Development and Regulation SL (Spain), the Covance Laboratories LTD group (UK) and Leanbio SL (Spain), which have provided the necessary expertise in nanotechnology and biotechnology, physicochemical characterisation, in vitro and in vivo biological evaluation, formulation and grading of nanomedicines, and pharmaceutical development and production under the guidelines of regulatory agencies.

CIBER and CSIC, promoters of orphan drugs

Orphan Drug Designations (ODDs) seeks to facilitate the arrival of treatments for rare diseases on the market. Several incentives are associated with ODDs, such as market exclusivity, fee reductions and specific scientific advice.

To date, CIBER has promoted eleven orphan drugs designated by the EMA, mainly from the thematic area of Rare Diseases (CIBERER), this being the first from CIBER-BBN.

On the other hand, this is the fourth ODD that the CSIC has obtained, and the first time it refers to a nanoformulated drug.

Orphan drug designation by the European Medicines Agency has several advantages, such as receiving a commercialisation authorisation for 10 years during which similar products cannot be commercialised, the availability of free or low-cost scientific advice and support protocols, and exemption from designation fees. In addition, entities developing orphan drugs have access to specific grants from the European Union and member states’ programmes.

More information

Scientific Culture Unit UCC+i CIBER cultura.cientifica@ciberisciii.es

Other related news

Smart-4-Fabry final workshop

Rare diseases Day February 29: combating Fabry Disease

Fabry disease & Smart4Fabry project

Lysosomal Rare Disorders: Focus on Fabry Disease

Fabry disease awareness month, April

“a-Galactosidase A Loaded Nanoliposomes with Enhanced Enzymatic Activity and Intracellular Penetration”

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An Auristatin-based nanoconjugate reduces leukemia burden in a disseminated AML model

Researchers of the Nanotoxicology Unit of the the CIBER-BBN ICTS NANBIOSIS (u18-nanotoxicology-unit), leaded by Ramon Mangues and Isolda Casanova at the Research Institute of the Hospital de Sant Pau and of the NANBIOSIS (nanbiosis.es) Protein Platform (u1-protein-production-platform-ppp) leaded by Antonio Villaverde and Neus Ferrer Miralles of the Institute of Biotechnology and Biomedicine at the Autonomous University of Barcelona, have developed a novel protein-Auristatin nanoconjugate that specifically targets CXCR4-overexpressing acute myeloid leukemia (AML) cells. It selectively accumulates in target cancer cells expressing this receptor and deliver the toxin Auristatin within their cytosol. There, Auristatin potently blocks microtubule polymerization, provoking mitotic catastrophe, followed by apoptotic induction. Since Auristatin can kill both cycling and quiescent cells, the administration of the nanoconjugate at repeated dosage is able to dramatically reduce the leukemia burden in circulating blood, bone marrow, liver and spleen; thus, producing a potent antineoplastic effect, in the absence of systemic toxicity.

It is known that CXCR4 overexpression is involved in bopne marrow colonization by leukemic cells, displacing normal hematopoietic stem cells, an effect that associates with quiescence, resistance to classical chemotherapy, development of minimal residual disease and relapse, which leads to shorter patient survival. Therefore, this Auristatin-based nanoconjugate could be a novel approach for the treatment of CXCR4-overexpressing AML that relapses after classical chemotherapy, offering hope to an effective clinical translation and industrial transfer, aqn activity that which could increase the effectiveness of AML treatment while reducing the adverse effect associated with current therapy.

Reference:

Pallarès V, Unzueta U, Falgàs A, Sánchez-García L, Serna N, Gallardo A, Morris GA, Alba-Castellón L, Álamo P, Sierra J, Villaverde A, Vázquez E, Casanova I, Mangues R. An Auristatin nanoconjugate targeting CXCR4+ leukemic cells blocks acute myeloid leukemia dissemination. doi: 10.1186/s13045-020-00863-9.

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New COVID-19 Diagnostic System Ready for Trials in Clinical Samples

The new system for the rapid, economic and efficient diagnosis of COVID-19 devised by the Universitat Politècnica de València (UPV), the IIS La Fe and the CIBER-BBN is now ready for trials on clinical samples. Since the pandemic broke out, the group of Professor Ramón Martínez Máñez, a researcher at the IDM Institute of the UPV and scientific director of the CIBER-BBN and NANBIOSIS U26 RNM for Biomedical Applications I, has been working on an alternative for the diagnosis of COVID-19, based on nanoporous films. These materials are capable of storing an indicator that is released only in the presence of the SARS-CoV-2 virus thanks to a system of molecular gates. And they do it very quickly, reliably and easily.

The material has already demonstrated its ability to detect the Spike protein present in SARS-CoV-2 and also its function for the detection of a model virus that expresses the aforementioned protein and that has been implemented by the Viral Biology group of the I2SysBio, center mixed of the University of Valencia and the Higher Council for Scientific Research (CSIC), led by Dr. Ron Geller.

“These advances represent another step towards obtaining the final device and confirming that the system is capable of recognizing virus particles”, highlights Ramón Martínez Máñez, director of NANBIOSIS U26 NMR for Biomedical Applications I.

The UPV team of researchers will carry out the clinical validation of the device in collaboration with Dr. Javier Pemán and Dr. Mª Ángeles Tormo, from the Serious Infection Research Group at IIS La Fe, by Dr. María Dolores Gómez, Head of the Molecular Microbiology Unit of the Microbiology Service of the Hospital Universitari i Politècnic La Fe and by Drs. Miguel Salavert and Eva Calabuig, of the Infectious Diseases Unit of the aforementioned hospital.

Once its sensitivity for the diagnosis of COVID-19 has been verified, it is planned to develop a final kit and obtain the CE marking, which will allow its commercialization. “We hope that this process will be carried out as quickly as possible and that it may be on the market to provide a new tool in the face of the pandemic that we are suffering,” says Dr. Elena Aznar, a researcher at CIBER-BBN.

Among the advantages of the device devised by the researchers of the UPV, UV, CSIC, IIS La Fe and CIBER-BBN, I would highlight its ease of use, being able to be used for the diagnosis of COVID-19 in places with limited infrastructure. Furthermore, it does not require highly qualified personnel and the sample does not have to be analyzed in specialized laboratories.

“In addition, the POC technologies on which it is based are global detection tools to monitor for possible new outbreaks in the future, so that once it is ready for use, it will contribute to the rapid implementation of containment measures”, he highlights Ramón Martínez Máñez.

The development of this project is financed by funds from the Covid-19 Donations of the Generalitat Valenciana, made by people and companies during 2020 to contribute to the fight against the pandemic. The solidarity of the Valencian citizenship materialized in donations of about 1 million euros, destined entirely to research projects of excellence against the virus such as the one led by Professor Martínez Máñez, managed by the Ministry of Innovation, Universities, Science and Society Digital.

The project also has the support of the Supera COVID-19 Fund, promoted by Crue Universidades Españolas, Banco Santander -through Santander Universidades- and the CSIC. In addition, the I2SysBio Viral Biology group (UV-CSIC) received funding from the Valencian Innovation Agency (AVI) for the implementation of the model virus.

A nanotoxin targeting the receptor CXCR4 blocks lymphoma dissemination

Researchers at the Nanotoxicology Unit of CIBER-BBN ICTS NANBIOSIS (u18-nanotoxicology-unit), led by Ramon Mangues and Isolda Casanova of the Research Institute at the Hospital de Sant Pau and the Researchers of the NANBIOSIS (nanbiosis.es) Protein Production Platform (u1-protein-production-platform-ppp) led by Antonio Villaverde and Neus Ferrer Miralles of the Institute of Biotechnology and Biomedicine at the Autonomous University of Barcelona, have participated in the development of a novel protein nanoparticle that incorporates the Exotoxin of the bacteria Pseudomonas aeruginosa, capable of targeting lymphoma cells that overexpress the CXCR4 receptor.

They internalize selectively in target cancer cells through CXCR4 receptor-mediated endocytosis due to the incorporation in its nanostructure of the T22 peptide ligand, with multivalent display (10 peptides per nanoparticle). In addition, it contains an endosomal escape domain to avoid lysosomal degradation to achieve the delivery of undegraded exotoxin in the target cancer cell cytosol. There, the exotoxin blocks protein translation by inhibiting the elongation factor 2, leading to the induction of apoptosis in a diffuse large B-cell lymphoma model blocking their dissemination throughout the body, in the bone narrow, lymph nodes and the liver. Since lymphoma cells overexpressing the CXCR4 receptor are associated with increased dissemination and resistance to Rituximab plus CHOP chemotherapy, this novel nanomedicine could be useful for its clinical translation, especially for the treatment of lymphoma patients that relapse after classical chemotherapy.

The bioluminescent follow-up of cancer cells and toxicity studies has been performed in the ICTS NANBIOSIS using its CIBER-BBN Nanotoxicology Unit Protein production has been also performed at the ICTS NANBIOSIS Init 1 PPP

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. doi: 10.7150/thno.43231. eCollection 2020.

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Gels formed from the interaction of lipid vesicles: Influence of charge in their structural and rheological properties

Susana Vilchez, researcher at NANBIOSIS U12. Nanostructured liquid characterization unit of CIBER-BBN and IQAC-CSIC, is coauthor of an article recently published in the Journal of Molecular Liquids.

“This work – explains Susana Vilchez – shows how structural and viscoelastic properties of a lipid colloidal gel can be altered by varying the ratio of charged lipids in the dispersion. These findings corroborate that the eventual formation of the gel and the morphology of its network is governed by the repulsive potential of the particles instead of the molecular composition of their membranes. Thus, the right control of charge balance in the system may allow finding specific applications for such material, especially in the biomedical field due to its lipid composition”.

Rheological measurements have been performed by the Nanostructured Liquids Unit (U12) of the ICTS NANBIOSIS.

Article of reference:

Kirian Talló, Susana Vílchez, Ramon Pons, Olga López. Gels formed from the interaction of lipid vesicles: Influence of charge in their structural and rheological properties. Journal of Molecular Liquids Volume 322, 15 January 2021, 114957 https://doi.org/10.1016/j.molliq.2020.114957

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Agreement signed with Spanish Government for the allocation of FEDER funds for NANBIOSIS ICTS units at JUMISC

In the framework of the FEDER Program in ICTS 2019 14 50, a project related to the ICTS NANBIOSIS has been selected by the Ministry of Science, Innovation and Universities for co financing with FEDER funds of the European Regional Development Funds program.

An agreement has been signed between Ministry of Science and Innovation and CCMIJU, institution for the co financing of the Project ICTS 2019 14 50 : Genética embrionaria en reproducción asistida (GENERA NANBIOSIS) in Unit 23.

The total budget of the project amounts to € 98.000, with 80% financing with FEDER Funds.

CCMIU is processing the necessary contracting procedures for the execution of this project.

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Identification of a novel nanotherapy active in cancer cells resistant to chemotherapy

Researchers of the Nanotoxicology Unit (u18-nanotoxicology-unit) led by Ramon Mangues and Isolda Casanova at the Research Institute of the Hospital de Sant Pau and the Protein Production Platform (u1-protein-production-platform-ppp), led by Antonio Villaverde and Neus Ferrer Miralles of the Institute of Biotechnology and Biomedicine at the Autonomous University of Barcelona, both belonging to the ICTS NANBIOSIS (nanbiosis.es) of the CIBER-BBN, have participated in the production of a novel Nanotoxin capable of selectively killing cancer cells which became resistant to chemotherapy. Development of cancer resistance frequently associates with the overexpression of the CXCR4 receptor.

It is known that chemotherapy kills cancer cells, mainly, by induction of apoptosis, after damaging the cell DNA; therefore, to survive resistant cancer cells develop anti-apoptotic mechanisms. In contrast, a Nanotoxin that has incorporated the exotoxin of Corynebacterium diphtheriae and a targeted ligand that selectively internalizes in CXCR4+ cancer cells, exploits a mechanism of cell death alternative to apoptosis, thus, effectively killing resistant cancer cells in a colorectal cancer model. The new mechanism is the induction of a blockade of protein translation, by inhibition of the elongation factor 2, which renders sensitive to therapy cancer cells resistant to chemotherapy.

The described work opens a new avenue for the exploration of antitumor activity in cancer that relapses after current therapy, an unmet medical need in oncology, and therefore, it could have an important impact in cancer patient well being.

Reference:

Naroa Serna, Patricia Álamo, Prashanthi Ramesh, Daria Vinokurova, Laura Sánchez-García, Ugutz Unzueta, Alberto Gallardo, María Virtudes Céspedes, Esther Vázquez, Antonio Villaverde, Ramón Mangues, Jan Paul Medema. Nanostructured toxins for the selective destruction of drug-resistant human CXCR4 + colorectal cancer stem cells. doi: 10.1016/j.jconrel.2020.01.019.

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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 Platform t
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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Nanbiosis

You are here : Home / 2021 (Page 10)

CCMIJU leads an European Project based on mixed reality and 3D printing applied to medical education

A more effective nanomedicine has been developed for the treatment of Fabry rare disease.

An Auristatin-based nanoconjugate reduces leukemia burden in a disseminated AML model

New COVID-19 Diagnostic System Ready for Trials in Clinical Samples

A nanotoxin targeting the receptor CXCR4 blocks lymphoma dissemination

Gels formed from the interaction of lipid vesicles: Influence of charge in their structural and rheological properties

Agreement signed with Spanish Government for the allocation of FEDER funds for NANBIOSIS ICTS units at JUMISC

Identification of a novel nanotherapy active in cancer cells resistant to chemotherapy

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

Agreement signed with Spanish Government for the allocation of FEDER funds for Nanbiosis ICTS