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

In the framework of the FEDER Program in ICTS 2014-2020, a projects 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, Innovation and CCMIJU, institution that houses NANBIOSIS  U14, U19, U21, U22, U23, U24 for the co-financing of the Project ICTS-2019-14-46: “ACTUALIZACIÓN DE LAS INFRAESTRUCTURAS E IMPLEMENTACIÓN DE UN SISTEMA DE CONTROL DOCUMENTAL Y DE GESTIÓN LIMS PARA POTENCIAR LAS CAPACIDADES DE LAS UNIDADES DE LA ICTS DISTRIBUIDA NANBIOSIS (AILIMS-NANBIOSIS)”

 The total budget of the project amounts to € 597.000, with 80% financing with FEDER Funds.

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

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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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Design and engineering of tumor-targeted, dual-acting cytotoxic nanoparticles

In the frame of the collaboration of three units of NANBIOSIS, researchers of CIBER-BBN Groups proposed a strategy to simultaneously deliver anticancer drug pairs, composed by a tumor-targeted protein nanoparticle and an antiproliferative drug, with specific activ-ity for the same type of cancer.

These three units are:

The results on the investigation have been published in an article entitled “Design and engineering of tumor-targeted, dual-acting cytotoxic nanoparticles”· by Acta Biomaterialia

The researchers have explored the possibility to conjugate tumor-targeted cytotoxic nanoparticles and conventional antitumoral drugs in single pharmacological entities using CXCR4-targeted self-assembling protein nanoparticles based on two potent microbial toxins, the exotoxin A from Pseudomonas aeruginosa and the diphtheria toxin from Corynebacterium diphtheriae, to which oligo-floxuridine and monomethyl auristatin E respec- tively have been chemically coupled.

The resulting multifunctional hybrid nanoconjugates, with a hydro- dynamic size of around 50 nm, are stable and internalize target cells with a biological impact. Although the chemical conjugation minimizes the cytotoxic activity of the protein partner in the complexes, the concept of drug combination proposed is fully feasible and highly promising when considering multiple drug treatments aimed to higher effectiveness or when facing the therapy of cancers with acquired resistance to classical drugs.

Thus, these results open a wide spectrum of opportunities in nanomedical oncology.

Article of reference:

Eric Voltà-Durán, Naroa Serna, Laura Sánchez-García, Anna Aviñó, Julieta M. Sánchez, Hèctor López-Laguna, Olivia Cano Garrido, Isolda Casanova, Ramón Mangues, Ramon Eritja, Esther Vázquez, Antonio Villaverde, Ugutz Unzueta Design and engineering of tumor-targeted, dual-acting cytotoxic nanoparticles. Acta Biomaterialia, Volume 119, 1 January 2021, Pages 312-322), 57746-57756 https://doi.org/10.1016/j.actbio.2020.11.018 

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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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New spin off of VHIR “BSURE Medical” led by Simó Schwartz (NANBIOSIS U20)

Dr. Simó Schwartz, Scientific Director of NANBIOSIS U20 and head of the “Drug Delivery and Targeting group” of CIBER-BBN and VHIR, toghether with Dr. Jaume Alijotas (VHIR), have promoted the creation of the Spin-off ·BSURE Medical· for the devlopment of products and services for the diagnosis, prevention and consultation of aspects related to treatments with all types of bioimplants.

One of the objectives of the Drug Delivery and Targeting group is to carry out preclinical studies to determine the effects and toxicities of drug delivery systems, cell therapies and biomaterials. Studies chace been carried out through the Nanbiosis unit U20, of which the CIBBIM-Nanomedicine platform for functional validation and preclinical studies (FVPR) is a part. The group’s interest in studying the immune-related adverse effects caused by different biomaterials, allowed the identification and validation in two clinical studies of the predictive use of specific genetic biomarkers associated with severe late responses caused by injectable biomaterials, the basis of the new company BSure Medical.

Dr. Jaume Alijotas and Simó Shwartz have led the development of a procedure that makes it possible to determine, reliably and easily the risk of suffering serious late-onset immune, local, regional or systemic adverse effects (edema, angioedema, induration of skin, multiple inflammatory nodules, panniculitis, even granulomatous or autoimmune diseases…) after implantation of an injectable biomaterial, such as dermal or subcutaneous fillers. This risk is strongly associated with the presence of certain antigen profiles in a biological sample of the individual, which allows them to be easily identified from the analysis of blood or saliva samples.

The technology is patented and has been validated in two independent clinical trials coordinated by the Systemic Autoimmune Diseases Unit of the Vall d’Hebron University Hospital in Barcelona and by the Dermatology Department of the Erasmus Medical Center, Rotterdam and the Department of Plastic Surgery, VU University Medical Center, Amsterdam. The VHIR has granted BSURE a license to use and exploit it exclusively and worldwide. The patent has already been granted in Europe, Brazil and Japan

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Encapsulation of BSA/alginate water–in–water emulsions by polyelectrolyte complexation

Researchers of NANBIOSIS U12. Nanostructured liquid characterization unit from CIBER-BBN and IQAC-CSIC have recently published an article entitled Encapsulation of BSA/alginate water–in–water emulsions by polyelectrolyte complexation in the scientific journal Food Hydrocolloids

The research which results are published involves the encapsulation of drops of water-in-water emulsions, which could be used as vehicles for the administration of active principles.

Characterization of emulsions and capsules was performed in the Unit 12 of NANBIOSIS Nanostructured Liquid Characterization Unit.

Water-in-Water (W/W) emulsions were prepared in aqueous mixtures of an anionic polyelectrolyte (sodium alginate, NaAlg), with a globular protein (bovine serum albumin, BSA). This combination showed phase separation at two different intervals of pH, and their phase behavior was studied. BSA-in-alginate emulsions were obtained and dropped into Ca2+, Fe3+ or chitosan solutions, forming capsules with diameters around 2–4 mm, by ionic complexation of sodium alginate, located in the continuous phase of the emulsions. The results showed a strong dependence on the cation or polycation. Capsules prepared with Ca2+ were not robust and collapsed during freeze-drying, while Fe3+ induced the gelation of the interior of capsules, even at short (5 min) contact time. Better results were obtained when encapsulating with chitosan and applying longer immersion times. In these capsules, the liquid interior contained well-preserved BSA-in-alginate emulsions droplets, identical to the initial emulsions before encapsulating. Freeze-dried spherical capsules prepared with alginate/Fe3+ or alginate/ chitosan shells had smooth surfaces, and a highly porous interior, templated by the presence of W/W emulsion droplets.

Article:

M. Michaux, N. Salinas, J. Miras, S. Vílchez, C. González-Azón, J. Esquena,
Encapsulation of BSA/alginate water–in–water emulsions by polyelectrolyte complexation, Food Hydrocolloids, Volume 113, 2021, 106406,

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Smart-4-Fabry final workshop

Next Wedneday, February 3, 2021 will take place the on-line event Smart-4-Fabry Final Workshop.  

Smart-4-Fabry is a european project, coordinated by CIBER-BBN wich has been developed during four years. This project is a sign of cooperation at European level to boost nanomedicine development and translation to clinical stages.

This project is also a clear example of the relevance of access to advanced research infrastructures as NANBIOSIS -ICTS. Four NANBIOSIS units have collaborated and contributed to Smart-4-Fabry development:

“The Fabry disease (FD) is a lysosomal storage disorder (LSD) that currently lacks an effective treatment” as Prof. Nora Ventosa, IP of the project, explained for NANBIOSIS blog – The aim of Smart-4-Fabry is to obtain a new nanoformulation of GLA, that will improve the efficacy and toleration compared to the actual treatment with non-formulated GLA.

In the final workshop experts will talk about how, why and for what the solution proposed by Smart4Fabry was conceived.

Registrations and program at https://smart4fabry.cientifis.com/

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New Center for Research in Advanced Pharmaceutical Development

The NanoBioCel Research group, led by Jose Luis Pedraz, from CIBER-BBN and UPV/EHU, group that coordinates the Unit U10 Drug Formulation of NANBIOSIS -ICTS, together with the Provincial Council of Álava and the Center for Technological Research and Development TECNALIA, have launched last Thursday, January 21, the new Center for Research in Advanced Pharmaceutical Development, which will be located in the Lascaray Building, on the Álava campus of the UPV / EHU.

The objective of this center is to introduce new technologies in the pharmaceutical field and promote applied research in 3D Bio-printing, 3D Printing of medical devices and 3D Printing of new drugs.

This new center is a strategic and ambitious project, supported directly by the Provincial Council of Álava with a budget of € 2,500,000 that seeks to integrate the Álava region within the strategy proposed by the European Union in biosciences and technological development, sectors that have been boosted in the new investment initiative in response to the Coronavirus. This center is also a regional reference as a result of the leadership exercised by the NanoBioCel research group and a fruitful relationship of common projects to offer services to the pharmaceutical industry with Tecnalia2.

In the picture: Jose Luis Elejalde from Tecnalia, Javier Hernando from the Provincial Council of Alava, Pilar Garcia de Salazar, Lieutenant General Deputy and Provincial Deputy for Economic Development and Territorial Balance in the Provincial Council of Alava. Jose Luis Martin, Vice-Rector for Research of the UPV / EHU and Jose Luis Pedraz, IP NanoBioCel group.

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