News U20

New therapeutic strategies for the treatment of advanced breast and colon cancer

Sara Montero, researcher of the “Drug Delivery and Targeting” of CIBER-BBN and VHIR, presented her thesis work on November 22 “Nanotecnnology mediated extrategies targeting cancer stem cells for advanced cancer tratment”, directed by Dr. Simó Schwrtz and Dr Diana Rafael.

In vivo experiments where carried out through the Unit 20 of the ICTS NANBIOSIS.

The work presented by Sara Montero shows two different types of therapeutic strategies for the treatment of advanced breast and colon cancer. Both strategies focus on blocking proteins essential for the survival and proliferation of cancer stem cells (CMC), known to be the main responsible for current therapeutic failures, tumor repopulation after treatments, as well as the causes of the aggressiveness of the resulting metastases. In addition, both strategies take advantage of the advantages offered by nano-drug delivery systems (nano-DDS) to increase the therapeutic efficacy of administered anticancer agents, reduce harmful side effects and, most relevant, specifically eliminating the CMC fraction within tumors. This project has also made it possible to evaluate the effects of combined therapy, using conventional drugs for the treatment of the disease together with specific molecules for the eradication of CMC in the same nanoplatform; specifically a system of polymeric micelles made up of the amphiphilic polymer Pluronic® F127. Together, this work opens the possibility of co-administering different types of compounds to simultaneously eliminate the two main cell populations that make up tumors and thus achieve complete tumor remission.

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Extracellular vesicles secreted by cancer stem cells promote angiogenesis and disease progression

Patricia González, researcher of the “Drug Delivery and Targeting” of CIBER-BBN and VHIR, presented her thesis work on November 19 where she lays the foundations to understand the role of different subpopulations of extracellular vesicles (VEs) secreted by tumor models in the regulation of tumor plasticity, as well as its effect on the tumor microenvironment and disease progression.

In the project, it has been described for the first time how the VEs secreted by the cancer stem cell subpopulation are responsible for activating fibroblasts in the tumor microenvironment and promoting angiogenesis, thus facilitating disease progression. Furthermore, it has been possible to discern the role of these vesicles in the regulation of cell plasticity. In this sense, the VEs from tumor stem cells would act as effectors of cell differentiation in contrast to the action of the VEs secreted by differentiated cancer cells, which would stimulate the acquisition of stem cell characteristics.

In order to carry out the in vivo experiments, the services of ICTS Nanbiosis were used, through the U20.

The results open a new line of research in the group with a long journey ahead, setting as main objectives the identification of the molecular actors responsible for the activities described above as well as the translation of said knowledge into specific therapeutic strategies.

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New strategies with nanoparticles to fight the most aggressive breast cancer

Breast cancer is the leading cause of death in women between the ages of 20 and 59, and despite the fact that its diagnosis and treatment have improved greatly in recent years, relapses and resistance to treatment leave some young patients without a therapeutic option. .

Tumor stem cells, from which the rest of cancer cells derive and are the cause of the most aggressive cancers, are especially resistant to conventional cancer treatments. In this line, researchers from the CIBER-BBN of the Drug Delivery & Targeting group and NANBIOSIS U20 at the Vall d’Hebron Research Institute (VHIR),, have developed a new therapeutic system where citral, an effective compound against tumor stem cells, is carried in nanoparticles biodegradable.

This study, published in the journal Nanomedicine under the direction of the CIBER-BBN group leader at VHIR Dr. Ibane Abasolo, details the process of incorporation of citral into nanoparticles (Pluronic F127 polymeric micelles), which stabilize the drug and they make it even more effective against tumor stem cells in experimental models of breast cancer. The work has had the technological support of Unit 20 of the singular scientific technical infrastructure (ICTS) Nanbiosis.

According to Marwa M Abu-Serie, an Egyptian researcher who has carried out the work during her stay at the VHIR, “we have verified that the combination of these polymeric citral micelles with paclitaxel, a first-line drug used in chemotherapy for the treatment of breast cancer is beneficial and could prevent recurrences ”.

Conventional cancer treatments, such as paclitaxel, tend to kill tumor cells that grow faster and not so much tumor stem cells, which grow slowly. The combination of citral micelles with paclitaxel has shown, in cell cultures, that it is capable of acting together both on tumor stem cells and on the rest, avoiding the increase that usually occurs in the proportion of tumor stem cells when treatment it is performed exclusively with cytostatic drugs such as paclitaxel.

The director of this work at the CIBER-BBN, Ibane Abasolo, considers that a hopeful path opens up to “improve the management of the most aggressive breast cancers, by being able to combine standard chemotherapy with nanoformulations”.

Therefore, citral nanoencapsulation allows not only a direct effect on tumor stem cells but also synergism with existing chemotherapeutics, paving the way towards the complete eradication of cancer, although “more studies will be needed to delve into the cellular mechanisms and molecular techniques of such synergy and to further validate the results of cell culture in appropriate animal models ”, considers the researcher.

Article of reference:

Marwa M Abu-Serie, Fernanda Andrade, Patricia Cámara-Sánchez, Joaquín Seras-Franzoso, Diana Rafael, Zamira V Díaz-Riascos, Petra Gener, Ibane Abasolo, Simó Schwartz Jr Pluronic F127 micelles improve the stability and enhance the anticancer stem cell efficacy of citral in breast cancerPMID: 34160295 [DOI]

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Ibane Abasolo new Scientific Director of unit 20 of NANBIOSIS

Ibane Abasolo, the Scientific Coordinator of NANBIOSIS U20 of the CIBER-BBN at the Vall d’Hebron Research Institute (VHIR), has been appointed new Scientific Director, replacing Simó Schwartz, who has recently assumed the Directorate of the Blood and Tissue Bank of Catalonia. With her, there are 11 women who are Scientific Directors of NANBIOSIS units (46%), with the incorporation of Nora Ventosa and Rosa Villa during the past year 2020. Ibane Abasolo has also been appointed IP of the CIBER group that coordinates unit 20 of NANBIOSIS. The female replacement in the leadership of the CIBER groups is one of the priorities of the consortium and all the recent IP substitutions of the CIBER-BBN have been appointed researchers as group leaders.

Ibane Abasolo obtained degrees in Biochemistry and Biology from the University of Navarra in 1997 and 1998, respectively. During her doctorate in the laboratories of Dr. Alfonso Calvo (CIMA, Pamplona) and Prof. Zhou Wang (Northwestern University, Chicago, USA), she studied the role of a peptide hormone, adrenomedullin, in the prostate cancer. Dr. Abasolo continued her postdoctoral training in the group of Prof. F.X. Real (IMIM, Barcelona), where she focused on the study of key factors on the progression of pancreatic cancer and the development of the cerebellum. During this time, she gained extensive experience in experimental mouse models, including all steps from the generation of new transgenic models, to the molecular and cellular characterization of existing ones. Later, Dr. Abasolo moved to the High Technology Institute (PRBB, Barcelona), where she was trained in molecular imaging techniques such as microPET, SPECT and CT.

Dr. Abasolo has been part of the CIBER-BBN since 2007, when she joined the group led by Dr. Schwartz at the Vall d’Hebron Hospital, where she launched the Functional Validation and Preclinical Research Area (FVPR) of the CIBBIM -Nanomedicine as a technological platform from which industry or academic groups can advance in the preclinical development of its compounds. In fact, FVPR is part of Unit 20 and the Singular Scientific Technical Infrastructure (ICTS) Nanbiosis and is certified with ISO9001: 2015.

As a researcher, Dr. Abasolo currently collaborates in 4 European projects (NoCanTher, EvoNano, Safe-Med-Tech and Mimic-Key) and leads many other national projects, focused on improving the treatment of lysosomal storage disorders (PI18 / 00871 from ISCIII and ExoProd funded by FIPSE) or in the study of the role of tumor stem cells in cancer progression (NanoDireCT, RETOS-Collaboration project). At CIBER-BBN, Dr. Abasolo directly coordinates 3 intramural projects and a recently awarded valorization project (ADVERT).

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Collaboration of two NANBIOSIS units in the Valorisation Project “ADVERT”

The Project ADVERT (Advanced Extracellular Vesicles for Enzyme Replacement Therapy) is a research valorisation project recently granted by CIBER.

The project pursues to advance the development of extracellular vesicles as treatments for lysosomal diseases, specially to bring new therapies to treat FABRY disease.

The ADVERT Project will count on the active particpation of two NANBIOSIS units of CIBER-BBN:

Unit 20 of the ICTS NANBIOSIS at Vall d’Ebrón Hospital, led by Ibane Abasolo, who coordinates the project.

Unit 1 Protein Production Platform (PPP), at the IBB-UAB, led by Neus Ferrer, throught the coordination in the project of José Luis Corchero.

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 valorisation projects is in its fourth edition, having already financed a total of fourteen projects.

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Extracellular vesicles as vehicles for therapeutic enzymes in lysosomal deposition diseases

Researchers of two CIBER-BBN units of the ICTS (Singular Scientific and Technical Infrastructures) NANBIOSIS, led by Ibane Abasolo the U20 located in the VHIR and the U6 in ICMAB-CSIC have participated in a study to improve the treatment of lysosomal disorders.

In recent years, enzyme replacement therapies (ERTs) based on the systemic administration of a functional version of the defective enzyme have gained clinical relevance as a treatment for lysosomal storage disorders (LSD). However, the systemic administration of these recombinant enzymes has negative aspects, such as their low stability and inadequate distribution to the affected organs that result in a limited efficacy of ERT. In this context, the Vall d’Hebron Research Institute (VHIR) has led a study that has analysed the use of extracellular vesicles as vehicles for therapeutic enzymes in this type of lysosomal storage disorders. This work, in which the CIBBIM-Nanomedicine, Drug Delivery and Targeting, led by Dr. Ibane Abasolo and investigator Guillem Pintos, and Neurovascular Diseases, led by Dr. Anna Rosell, of the VHIR have participated, has been published in the Journal of Extracellular Vesicles.

Lysosomal storage disorders are rare congenital diseases caused by the lack or malfunction of proteins involved in lysosomal biogenesis and activity. In the absence of activity of these proteins, lysosomes accumulate waste molecules inside. Although there are more than seventy types of LSD – among which are the Gaucher, Fabry, Pompe and Sanfilippo syndromes – all of them share the abnormal accumulation of molecules such as glycoproteins, glycosaminoglycans and sphingolipids, something that in the majority of the cases generates serious clinical manifestations.

“The symptoms that the patient may experience depend on the specific disorder they develop, but in general LSDs results in a systemic disease that can affect multiple organs, including the central nervous system, liver, kidneys, heart and musculoskeletal system”, says Dr. Ibane Abasolo, principal investigator of the research group in CIBBIM-Nanomedicine, Drug Delivery and Targeting of the VHIR and author of the study. All LSDs are rare diseases and their low incidence makes it difficult to develop new therapies and evaluate them in clinical trials. For all these reasons, the VHIR has wanted to participate in this work, which has analysed and tested the viability of a new therapy for this type of lysosomal storage disorders. Specifically, for Fabry and Sanfilippo A diseases, two of the LSDs with the highest prevalence.

The study has obtained extracellular vesicles loaded with therapeutic enzymes directly from cells that are used for the production of recombinant protein. Extracellular vesicles have been shown to function as highly efficient protein delivery platforms, also in the brain, an organ that is not naturally accessed by systematically administered proteins. Dr. Abasolo considers that “the results obtained in this work will lay the foundations for the implementation of replacement therapy driven by extracellular vesicles in different LSDs, and will open the way for a possible treatment strategy in disorders with central nervous system involvement”.

The following centres have also participated in this work: Institute of Biotechnology and Biomedicine of the Autonomous University of Barcelona (IBB-UAB), Centre for Biomedical Research in Network of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Institute of Bioengineering of Catalonia (IBEC), Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), and Centre for Biomedical Research in Network on Liver and Digestive Diseases (CIBEREHD).

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Simo Schwartz: new General Director of the Bank of Blood and Tissues of Catalonia.

Simó Schwartz Jr., Scientific Director of NANBIOSIS Unit 20 In Vivo Experimental Platform has been appointed as the new general director of the Bank of Blood and Tissues of Catalonia, replacing Enric Argelagués, who is leaving his post after 17 years as director. Argelagués was the promoter of the unification of blood banks that began in the eighties and culminated in the current Bank of Blood and Tissues of Catalonia.

Simó Schwartz now assumes the executive management of the organization, which currently has more than 800 workers and its mission is to ensure that all people in Catalonia have the blood and tissues necessary for their treatment at their disposal, promoting proper use. It is a reference center in diagnostic immunology and in the development of advanced therapies, it is present in the main hospitals in Catalonia and is part of the national and international organizations related to donation, transfusion and treatments with biological components.

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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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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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Nanoparticles to eradicate Cancer Stem Cells

Colorectal cancer (CRC) has a high prevalence worldwide and resistance to conventional chemotherapies and tumor relapse are usually related with a population of cells with malignant properties – Cancer Stem Cells (CSC).

Scientists of CIBER-BBN and VHIR have led a research with the goal not only to treat the primary CRC, but also eradicate CSC. For both purposes, the use of nanoparticles (NP) is a useful strategy. These “bullets” carrying a drug in its core, are able to reach tumor tissue due to its small size. Cancer cells, and in particular CSC, present at their surface receptors that could be specifically recognized by molecules used to decorate NP, driven the drug of interest to these cells. In this work we developed a type of NP decorated with an antibody fragment that specifically recognize the receptor CD44v6, which is overexpressed in CSC and was previously demonstrated to be present in patients with metastasis and poor-prognosis. Moreover, researchers have encapsulated Niclosamide (NCS), a drug that demonstrated efficacy against breast CSC, inside their NP. NP increased the efficacy of NCS and accumulated in the tumors reducing its systemic exposure and increasing safety. Most importantly, the developed system significantly reduce circulating tumor cells, precursors of metastasis, reducing CSC malignancy.

This system has the potential to create a new therapeutic approach that could bring a new hope for CRC treatment and prevention of cancer relapse.

The work has been developed at the group of CIBBIM-Nanomedine_Drug Deliver & Targeting of Vall d’Hebron Institute of Research (VHIR) and CIBER-BBN, in collaboration with Bruno Sarmento (University of Porto, Portugal) and Marika Nestor (Uppsala University, Sweden) that helped to developed the NP and the targeting antibody, respectively. In vivo assays on the safety and efficacy of the NPs were conducted thanks to the contribution of the FVPR/U20 of ICTS-Nanbiosis.

Article of reference

Fernanda Andrade, Diana Rafael, Mireia Vilar-Hernández, Sara Montero, Francesc Martínez-Trucharte, Joaquin Seras-Franzoso, Zamira V.Díaz-Riascos, Ana Boullosa, Natalia García-Aranda, Patricia Cámara-Sánchez, Diego Arango, Marika Nestor, bane Abasolo, Bruno Sarmento, Simó SchwartzPolymeric micelles targeted against CD44v6 receptor increase niclosamide efficacy against colorectal cancer stem cells and reduce circulating tumor cells in vivo Journal of Controlled Release Volume 331, 10 March 2021, Pages 198-212 https://doi.org/10.1016/j.jconrel.2021.01.022

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