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News U3

News U3

Impactful research with NANBIOSIS participation in the Poster Tour of CIBER-BBN & CIBEREHD Annual Conference.

2023 CIBER-BBN Annual meeting has taken place at Santemar Hotel, in Santander during November 6-7. This year the format of our annual conferences has been changed towards a collective event scheme between the CIBER-BBN and CIBEREHD thematic areas.

  • On Monday 6 the scientific sessions werecommon for EHD and BBN, with appealing contents for the mixed audience.
  • On Tuesday 7 EHD and BBN sessions will specific for each area in separate rooms (with common coffee break).

Posters of both areas were on display in the exhibit hall throughout the entirety of the Annual Meeting.

Moreover, at the “Posters & beers” session (Monday 6th: 6:00 p.m. – 7:00 p.m.) poster tours were organized where attendees could cast their vote for the best poster and use this one-on-one time with presenters to learn more, ask juicy questions and discuss their work. At 8:00 p.m., the awards ceremony took place for the best oral communication and best poster by young authors – for each area.

It was an impactful information sessions on research carried out by the groups of CIBER-BBN and CIBEREHD thematic areas.

The poster session is always a popular feature at CIBER-BBN Annual Meeting for acknowledgment NANBIOSIS units’ participation in the research carried out during the year. These are the works presented in 2023:

Targeted nanotoxin for the selective depletion of CXCR4+ cancer cells and immune cell recruitment in a colorectal cancer mouse model. Luis Miguel Carrasco-Díaz, Naroa Serna, Eric Voltà-Durán, Ugutz Unzueta, Esther Vázquez, Antonio Villaverde, Patricia Álamo, Lorena Alba-Castellón, Ramón Mangues. With participation of NANBIOSIS Units U1 Protein Production Platform (PPP) and U18 Nanotoxicology Unit . (Contact:
luismiguelcarrascodiaz@gmail.com)

Improvement of the biodistribution of GLA enzyme by RGD-functionalized nanoGLA in a Fabry mouse model.
Zamira Vanessa Diaz Riascos, Marc Moltó Abad, Daniel Marijuan, Belen García Prats, Judit Tomsen Melero, Elisabet González Mira, Jose Luis Corchero, Andreu Soldevila, Miriam Royo, Alba Córdoba, Nora Ventosa, Guillem Pintos Morell, Simo Schwartz , Ibane Abasolo. With participation of the NANBIOSIS units U20 FVPR-In Vivo Experimental Platform, U3 Synthesis of Peptides Unit and U6 Biomaterial Processing and Nanostructuring Unit. (Contact:
vanessa.diaz@vhir.org)

An auristatin-based nanoconjugate induces apoptosis and inhibits the bone marrow leukemia burden in an acute myeloid leukemia mouse model. Annabel Garcia-León, Julián I. Mendoza, Ariana Rueda, Luis Carlos Navas, Vanessa Huaca, Ugutz Unzueta, Jorge Sierra, Esther Vázquez, Antonio Villaverde, Ramon Mangues, Isolda Casanova. With participation of NANBIOSIS Units U1 Protein Production Platform (PPP) and U18 Nanotoxicology Unit. (Contact: agarciale@santpau.cat)

FVPR/U20-NANBIOSIS Service Platform: from the Synthesis and Characterization of Nanotechnology-based Therapies, to the in vitro and in vivo Preclinical Validation. Diana Rafael, Zamira V. Diaz Riascos, Belén García, Alejandra Palacios, Sandra Mancilla, Laura Garcia, Ibane Abasolo. Description of NANBIOSIS Unit 20 FVPR-In Vivo Experimental Platform. (Contact: diana.fernandes_de_so@vhir.org)

Non-Viral Vector Development for Gene Therapy in the Treatment of Congenital Liver Metabolic Diseases Lucía Enríquez Rodríguez, Isabel Carbonell Simón, Idoia Gallego Garrido, Virginia Nieto Romero, Iván Maldonado Pérez, Aida Garcia Torralba, Gustavo Puras Ochoa, Miruna Giurgiu, Jose Carlos Segovia Sanz, María García Bravo, Oscar Quintana Bustamante, José Luis Pedraz Muñoz. With participation of NANBIOSIS U10 Drug Formulation unit. (Contact: lucia.enriquez@ehu.eus)

X-ray Photoelectron Spectroscopy (XPS) Analysis of Nitrogen Environment in Small Extracellular Vesicle Membranes: A Potential Novel Technique with Application for Cancer Screening.
Ana Martín-Pardillos, María Sancho-Albero , Silvia Irusta , Víctor Sebastián , Vicente Luis Cebolla , Roberto Pazo-Cid , Pilar Martín-Duque , Jesús Santamaría. With participation of NANBIOSIS U9 Synthesis of Nanoparticles Unit. (Contact: a.martin_pardillos@unizar.es)

Nanoparticle-based approach for blood-brain-barrier crossing and glioblastoma treatment. Júlia German-Cortés, Raquel Herrero, Diana Rafael, Ibane Abasolo, Fernanda Andrade. With participation of NANBIOSIS Unit 20 FVPR-In Vivo Experimental Platform. (Contact: fernanda.silva@vhir.org)

Exploiting mammalian cells for recombinant protein production: an improved protocol for transient gene expression. Aida Carreño Fibla, Roger Fernández Palomeras, José Luis Barra, Rosa Mendoza Moreno, Mercedes Márquez Martínez, Neus Ferrer-Miralles, Antonio Villaverde Corrales, José Luis Corchero Nieto. With participation of NANBIOSIS Units U1 Protein Production Platform (PPP). (Contact:jlcorchero@ciber-bbn.es)

Surface characterization of a PLA/Qr/Mg biocomposite after in vitro degradation in m-SBF. Juan Manuel Casares-López, Margarita Hierro-Oliva, Verónica Luque-Agudo, Amparo M. Gallardo-Moreno, María Luisa González-Martín. With participation of Unit 16 Surface Characterization and Calorimetry Unit (Contact: mlglez@unex.es)

The poster session was an effective forum for the exchange of information and a means to communicate ideas

Related news:

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New nanoarchitectonics of RGD peptide developed using quatsomes as robust tool in tissue engineering.

Researchers of three groups of CIBER-BBN at CSIC and IBEC, have created a versatile platform based on hierarchically nanostructured RGD peptide using quatsomes, with proved enhanced cell adhesion. These findings, which arose within the framework of the intramural project of CIBER-BBN “Molecular Biointerfaces for cell guidance” (DynaMo4Vasc), open new possibilities for tissue engineering.

The participation of two NANBIOSIS units were acknowledged in the publication of the research results: the synthesis of RGD derivatives were performed at NANBIOSIS U3 “Synthesis of peptides unit” of CIBER-BBN at IQAC−CSIC.  And the design and characterization of quatsomes were done at U6 of NANBIOSIS “Biomaterial Processing and Nanostructuring Unit” of CIBER-BBN at ICMAB-CSIC.

Tissue Engineering and cell adhesion

Tissue engineering pursues the development of functional and easy biological substitutes that allow restoring damaged organ or tissue or maintaining their normal function. The newer approach is the combination of appropriate cells and growth factors with a scaffold that supports the tissue or organ.

The scaffold is crucial since it must provide the conditions and the environment for the adequate cell regulation (adhesion, migration, proliferation, and differentiation), as well as the adequate delivery of bioactive factors (growth and adhesion), so that cells form the new tissue with its proper structure and function.

Cell adhesion (the interaction of the cells with its surroundings) is an important phenomenon for the development of appropriate scaffolds for tissue engineering, as it can ultimately determine cell fate. Thus, the study of the factors that govern cell adhesion and its optimization is essential.

The tripeptide Arg-Gly-Asp (RGD) is the most common peptide responsible for cell adhesion. Although the studies of its surface density and spacing at nanoscale have already shown a significant influence on cell adhesion, the impact of its hierarchical nanostructure is still unexplored.

Quatsomes

Quatsomes are non-liposomal nanovesicles which have been shown to be very homogeneous and stable in different media and which can be easily tuned with a wide range of chemical functionalities.

The Nanomol Group (from CIBER-BBN and ICMAB-CSIC) has been working during the last years with these nanoparticles showing their suitability for applications in nanomedicine, (as nanocarriers and nanocontainers to encapsulate drugs and protein cargoes, or as fluorescent dyes for therapy and diagnostics). This expertise led the researcher to explore the integration of quatsomes with relevant molecules and their use once anchored to a surface.

RGD Nanoarchitecnonics

Nanoarchitectonics is a novel concept that refers to multicomponent systems organized through the supramolecular union of nanometer structures where the main players are not the individual nanoparticles but their interactions, giving rise to new functionalities.

The team of researchers developed a versatile platform based on quatsomes as an effective nanoscopic building block to achieve hierarchical nanostructures of the RGD peptide which were further anchored to gold substrate. In comparison with substrates featuring a homogeneous distribution of RGD peptides, the resulting hierarchical nanoarchitectonic surfaces dramatically enhanced cell adhesion.

These findings open many possible pathways for the understanding of cell behaviour and improve the performance of clinical applications like implants and tissue engineering.

Article of reference:

Marc Martínez-Miguel, Miquel Castellote-Borrell, Mariana Köber, Adriana R. Kyvik, Judit Tomsen-Melero, Guillem Vargas-Nadal, Jose Muñoz, Daniel Pulido, Edgar Cristóbal-Lecina, Solène Passemard, Miriam Royo, Marta Mas-Torrent, Jaume Veciana, Marina I. Giannotti, Judith Guasch, Nora Ventosa, and Imma Ratera. “Hierarchical Quatsome-RGD Nanoarchitectonic Surfaces for Enhanced Integrin-Mediated Cell Adhesion” ACS Appl. Mater. Interfaces 2022, 14, 42, 48179–48193 Publication Date:October 17, 2022 https://doi.org/10.1021/acsami.2c10497

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Happy Day of Chemistry! The role of Chemistry in a sustainable research in health

Today, November 15 is a day of celebration for us, the Day of the Chemistry in Spain!

Chemistry is the science that studies matter, how it is composed, its properties and how its structures are transformed and, as matter is everything, including living beings and ourselves, we can say that chemistry is omnipresent and transversal in all areas surrounding us. Chemistry is everywhere, we ourselves are chemistry and our health and our life is chemistry.

Everything around us is chemistry in the environment, foods, what we use and what we touch every day. Our own body is a sophisticated complex factory with an infinite number of chemical processes taking place on a perfect and synchronized manner”- points Pilar Marco, Scientific Director of NANBIOSIS U2 Custom Antibody Service (CAbS) from CIBER-BBN at IQAC-CSIC.

The crucial role of chemistry in everyday life is also evidence in the development of current technology and the economy. According the VCI Prognos Study, the Global growth forecast for Industrial Sectors, places the chemical industry in the fist position. As far as national picture, the INE Statistics on R+D Activities 2020 -last publish report-, chemical and pharmaceutical industry employs the 22,2 % of research staff recruited and the investment and expenditure on the chemical and pharmaceutical industry represents the 23,6% R+D and Innovation -above the motor vehicles industry.

Thanks to chemical and pharmaceutical research,

medicines, vaccines and health products have made great strides in fighting diseases and improving quality of life. Thanks to chemical and pharmaceutical medicine research, in few years, it will be possible, for example, to count on smart implants delivering personalised drugs only where cancer or infections are detected or biosensors circulating in our body to find diseases only one week after infection.

At the Institute of Advanced Chemistry of Catalonia, four NANBIOSIS units of CIBER-BBN use chemistry to deliver new therapeutic and diagnostic approaches that improve the quality of life of the society.

One of the research lines of the Nb4D group-U2 CabS at IQAC-CSIC (led by Pilar Marco and Nuria Pascual) focuses on the chemical signals that bacteria emit to communicate with each other and thus develop virulence mechanisms. Their knowledge will allow the development of new therapeutic and diagnostic strategies to mitigate the serious problem of antimicrobial resistance.

NANBIOSIS U3 Synthesis of Peptides UnitMS4N group, led by Miriam Royo, explores the use of diverse types of chemical multivalent platforms (oligomers, dendrimers, polymers, micelles and lipid nanovesicles) for the development of drug delivery systems for cancer treatment, protein delivery systems for the treatment of lysosomal diseases and macromolecular compounds that have intrinsically therapeutic properties with application to central nervous system diseases.

Chemistry plays an essential role in helping society achieve Sustainable Development Goals (SDGs)

In 2015 the United Nations created a universal call to action to end poverty, protect the planet, and ensure that all people enjoy peace and prosperity by 2030. This framework, comprising 17 aspirational goals known as the Sustainable Development Goals (SDGs)

Chemistry is key to achieve the SDG 3: Good Health & Well-Being with the development of new technologies that will provide a deeper understaunding of human health, making posible better, cheeper and faster medical diagnosis and treatmens.

In this sense, Carlos Rodriguez Abreu, Scientific Director of NANBIOSIS Unit for the characterization of nanostructured liquids (U12) explains: “The goals of sustainable development are producing a shift towards surfactants not based on petroleum derivatives, but derived from other raw materials that are more biocompatible and that allow a circular economy that is less aggressive with the environment. Quality control is necessary with regard to the properties of the products that contain surfactants, such as the droplet size in emulsions, the particle size in suspensions, their colloidal stability over time, among others. Additionally, products must be precisely formulated to optimize the use of raw materials and obtain the desired properties. In this context, the NANBIOSIS U12, acredited with ISO 9001:2015 by AENOR, offers a wide range of advanced analysis techniques for the determination of different colloidal properties such as droplet size and particle size, colloidal stability, viscosity, surface tension, pore size distribution, and determination of phase behavior and structure for the tailor-made formulation of surfactant and colloid systems for pharmaceutical and biomedical applications.

The Nucleic Acid Chemistry group at IQAC-CSIC – NANBIOSIS U29 Oligonucleotide Synthesis Platform (OSP) is developing new compounds based in DNA and RNA to detect and treat diseases participating in several projects with several research and industrial partners such as La Marato de TV3 (Covid), Oligofastx, Caminan2, Osteoatx. These new drugs use the natural mechanisms for gene regulation to treat undruggable diseases such Muscular dystrophy and others. Importantly special attention is made to design novel synthetic protocols to produce less organic waste what contributes to the sustainable development. 

We wish to all the family of chemistry professionals new projects and inspiration to achive humans Good Health & Well-Being and keep the world moving!

And Happy Chemistry Day, too, for all the chemistry enthusiasts!

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1st Nanomedicine Forum of CIBER-BBN/NANBIOSIS and CSIC Nanomed Conection

During the days 30 of June and 1st of July took place in Barcelona, in the auditorium of the Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), the 1st Forum on Nanomedicine gathering scientists from the CSIC net Nanomed Conection and from the CIBER-BBN and its ICTS NANBIOSIS.

This forum brought toguether researchers from the most eminent national research centers in nanomedicine, that during the two days meeting presented their works and findings and discussed the impact of nanomedicine in the fields of drug delivery, diagnosis and therapy.

The workshop was open by the Director of IQAC-CSIC,  Jesús Joglar, the  Scientific Coordinator of Nanomed Conection, Fernando Herranz, and the Scientific Director of CIBER-BBN, Ramón Martínez Máñez.

18 research groups gave their talks distributed in four sessions:

  • Nanobiotechnological solutions for diagnosis and therapy
  • Drug delivery nanosystems
  • Applications for oncology 
  • Nanomedicine & other frontier applications

The presentations aroused great interest and futher debate among the attendees present in the auditorium (around 50) and the on line participants (The event was also broadcast online previous registration with more than 125 registrations received).

The videos of the presentations will be soon available in the NANBIOSIS youtube channel.

Here we highlight the eight talks by researchers from NANBIOSIS units:

The first session of Nanobiotechnological solutions for diagnosis and therapy,  started  with the talk by Montserrat Rodríguez from Nb4D group NANBIOSIS U2 CAbS, from CIBER-BBN and IQAC-CSIC, entitled “Targeting aromatic amino acid metabolism for the early diagnosis of neurological diseases”, presenting their results on in vitro samples, on thermal power characterization experiments to study the thermal efficiency of non-sinusoidal stimulation and on efficiency characterization experiments in cell cultures with cancer cell liness.

Also in this session chaired by Miriam Royo, Scientific Coordinator of NANBIOSIS U3 Synthesis of Peptides Unit of  CIBER-BBN and IQAC-CSIC,  took place an interesting and passionate talk by Ramón Eritja, Scientific Director of NANBIOSIS U29 Oligonucleotide Synthesis Platform (OSP)

In the last years, interest in therapeutic applications of oligonucleotides has increased enormously, especially after the development of messenger RNA vaccines in response to the COVID-19 pandemic. In this way, metabolic diseases such as dyslipidemia and hereditary diseases such as Duchenne muscular dystrophy have been successfully addressed. The NANBIOSIS  Oligonucleotide Synthesis Platform (OSP) focuses on the design, synthesis and characterization of modified oligonucleotides, in order to enhance the therapeutic properties of the oligonucleotides and to improve the control of gene expression. Ramon Eritja presented their most recent results in the development of new conjugates with antiproliferative activity and in the design of DNA probes for the detection of viral genomes.

 

In the session of “Nanomedicine and other frontiers applications”, chaired by María del Puerto Morales Herrero (ICMM-CSIC), Elena Martínez Fraiz,  from the Nanobioengineering group of CIBER-BBN and IBEC running NANBIOSIS Unit 7 of Nanotechnology, presented  a nanostructured surface able to produce multivalent effects of surface-bound ephrinB1 ligands on the dynamics of oligomerization of EphB2 receptors  whic can benefit applications such as the design of new bioactive materials and drug-delivery systems.

The session of Drug delivery nanosystems, chaired by Ramón Martínez Máñez, began with the talk by Vanessa Díaz Riascos, presesnting the in vivo efficacy, biodistribution and toxicity testing of nanomedicines at NANBIOSIS U20 FVPR, of CIBER-BBN and VHIR, explaining how their texting expertise and their in vivo and ex vivo fluorescence imaging techniques facilitate a rapid and efficient preclinical development of candidates, reducing considerably the time and costs of conventional developments.


Santiago Grijalvo Torrijo, from NANBIOSIS U12 Nanostructured liquid characterization unit expoke about Nano-emulsion-derived polymeric carriers for biomedical applications also discussing the impact of the protein corona on colloidal stability, antioxidant activities, cytotoxicity and cellular uptake of drug-loaded nanoparticles.

Antoni Llopis Lorente, (NANBIOSIS U26 NMR: Biomedical Applications II), expoke about Gated silica nanoparticles for controlled release. Chemical communication, based on the exchange of molecules as messengers, allows different entities to share information, cooperate and orchestrate collective behaviors. Communication using chemical messengers (such as neurotransmitters, hormones and pheromones) is the main way of communication across the natural world; yet engineering chemical communication between micro/nanosystems is a key emergent topic in micro/nanotechnology, biomimicry and related areas. Santiago explainined recent progress by their group in the development of engineered particles for chemical communication and nanomedicine applications.

And closing the session, Mariana Köber (Nanomol Group –NANBIOSIS U6 of Biomaterial Processing and Nanostructuring Unit  from CIBER-BBN and ICMAB-CSIC) gave a talk on Quatsomes as versatile nanovesicles for biomedical applications.

In the session of Applications for Oncology, Pilar Martín Duque from NFP group – NANBIOSIS U9 Synthesis of Nanoparticles Unit of CIBER-BBN and INMA-CSIC, gave a very interesting talk explained their approach and recent progress on the search of trojan horses for an improved theragnosis of cancer.

Here we want to thank the Institute of Advanced Chemistry of Catalonia (IQAC-CSIC) for hosting this event and for the help in its preparation and development.

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Fabry Desease in the Rare Disease Day: A New Hope

WHY DO CELEBRATE TODAY THE INTERNATIONAL #RareDiseaseDay?

29 of February is a ‘rare’ date and February, a month with a ‘rare’ number of days, has become a month to raise awareness about rare diseases and their impact on patients’ lives.  Since 2008 thousands of events happen every year all around the world and around the last day of February with the aim of improving equity and reducing stigmatization for people who live with more than 6,000 rare diseases.

WHAT ARE RARE DISEASES

Rare diseases are pathologies or disorders that affect a small part of the population (less than 5 per 10,000 inhabitants) and generally have a genetic component. They are also known as orphan diseases.

Diseases present a series of particular symptoms, and it is very difficult to diagnose what their true cause is. These disorders or alterations that patients present must be evaluated by a specialist, depending on each case.

Today 5% of the world population suffer from them. This translated into numbers, corresponds to approximately 300 million affected.

A patient with a rare disease waits an average of 4 years to obtain a diagnosis, in 20% of cases it takes 10 or more years to achieve the proper diagnosis.

ORPHAN DRUGS

To combat this disease, patients need to be treated with so-called orphan drugs. They serve to prevent and treat pathology. Its composition is based on biotechnological compounds whose manufacture is very expensive and not profitable for companies. For this reason, cooperation of governments is needed as well as financial incentives to encourage pharmaceutical companies to develop and market medicines to make these treatments accessible to a greater number of people.

FABRY DISEASE

Fabry is one of the rare diseases that currently lack a definitive cure. Symptoms may include episodes of pain, especially in the hands and feet (acroparesthesias); small dark red spots on the skin called angiokeratomas; decreased secretion of sweat (hypohidrosis); opacity of the cornea (cataracts) and hearing loss. Internal organs such as the kidney, heart, or brain may be involved, resulting in progressive kidney damage, heart attacks, and strokes.

Fabry disease is a lysosomal storage disease arising from a deficiency of the enzyme α-galactosidase A (GLA). The enzyme deficiency results in an accumulation of glycolipids, which over time, leads to cardiovascular, cerebrovascular, and renal disease, ultimately leading to death in the fourth or fifth decade of life. Currently, lysosomal storage disorders are treated by enzyme replacement therapy (ERT) through the direct administration of the missing enzyme to the patients.

SMART 4 FABRY” EUROPEAN PROJECT

CIBER-BBN, through the researcher Nora Ventosa has coordinated the european project “Smart-4-Fabry” developed during 2017-2021, the proyect was undertaken by a consortium formed by ten partners, including private companies and public institutions in Europe and Israel, with a Horizon 2020 financial programme by the European Commission (H2020-NMBP-2016-2017; call for nanotechnologies, advanced materials, biotechnology and production; Proposal number: 720942-2).

In view of their advantages as drug delivery systems, liposomes are increasingly being researched and utilized in the pharmaceutical, food and cosmetic industries, but one of the main barriers to market is their scalability.

Depressurization of an Expanded Liquid Organic Solution into aqueous solution (DELOS-susp) is a compressed fluid-based method that allows the reproducible and scalable production of nanovesicular systems with remarkable physicochemical characteristics, in terms of homogeneity, morphology, and particle size. The objective of this work was to optimize and reach a suitable formulation for in vivo preclinical studies by implementing a Quality by Design (QbD) approach, a methodology recommended by the FDA and the EMA to develop robust drug manufacturing and control methods, to the preparation of α-galactosidase-loaded nanoliposomes (nanoGLA) for the treatment of Fabry disease.

Through a risk analysis and a Design of Experiments (DoE), researechers obtained the Design Space in which GLA concentration and lipid concentration were found as critical parameters for achieving a stable nanoformulation. This Design Space allowed the optimization of the process to produce a nanoformulation suitable for in vivo preclinical testing.

The new nanoformulation developed by Smart4Fabry for the treatment of Fabry disease achieved the ODD (Orphan Drug Designation) by the European Commission. The new nanomedicine is more effective and has a better biodistribution than the current treatments, based on enzyme replacement. The new nanomedicine is based on a nanovesicle that protects the enzyme and achieves a better cell internalisation, thus reducing the doses needed, the total cost and improving the quality of patients.

Four units of NANBIOSIS participated in the project:

– U1 Protein Production Platform (PPP) led by Neus Ferrer and Antony Villaverde at IBB-UAB for the production and purification in different expression systems for R&D purposes.

– U3 Synthesis of Peptides Unit led by Miriam Royo at IQAC-CSIC performed all the chemical process of the Smart-4-Fabry project, i.e. design and synthesis of peptides used as targeting ligands in the nanoliposome formulation.

– U6 Biomaterial Processing and Nanostructuring Unit led by Nora Ventosa at ICMAB-CSIC developed tasks related to the manufacture of the nanoliposome formulation of GLA enzyme and the physico-chemical characterization (this unit counts with plants at different scales, from mL to L, which allow process development by QbD and process scale-up, as well as instrumental techniques for assessment of particle size distribution, particle concentration, particle morphology and stability, and Z-potential) .

– U20 In Vivo Experimental Platform led by Ibane Abásolo at VHIR carried out the non-GLP preclinical assays of the project (in vivo efficacy, biodistribution and tolerance/toxicity assays).

PHOENIX: OPEN INNOVATION TEST BED

Researchers of CIBER-BBN and NANBIOSIS, led by Nora Ventosa, are currently participating in another european project, PHOENIX “Enabling Nano-pharmaceutical Innovative Products” in the framework of which this novel nanomedicine developed under the Smar4Fabry project and designed as Orphan Drug by the EMA, will be scaled-up and manufactured under GMP to enable its clinical testing.

Articles of reference:

Josep Merlo-Mas, Judit Tomsen-Melero, José-Luis Corchero, Elisabet González-Mira, Albert Font, Jannik N. Pedersen, Natalia García-Aranda, Edgar Cristóbal-Lecina, Marta Alcaina-Hernando, Rosa Mendoza, Elena Garcia-Fruitós, Teresa Lizarraga, Susanne Resch, Christa Schimpel, Andreas Falk, Daniel Pulido, Miriam Royo, Simó Schwartz, Ibane Abasolo, Jan Skov Pedersen, Dganit Danino, Andreu Soldevila, Jaume Veciana, Santi Sala, Nora Ventosa, Alba Córdoba, “Application of Quality by Design to the robust preparation of a liposomal GLA formulation by DELOS-susp method”, The Journal of Supercritical Fluids, Volume 173, 2021, 105204, https://doi.org/10.1016/j.supflu.2021.105204.

Judit Tomsen-Melero, Solène Passemard, Natalia García-Aranda, Zamira Vanessa Díaz-Riascos, Ramon González-Rioja, Jannik Nedergaard Pedersen, Jeppe Lyngsø, Josep Merlo-Mas, Edgar Cristóbal-Lecina, José Luis Corchero, Daniel Pulido, Patricia Cámara-Sánchez, Irina Portnaya, Inbal Ionita, Simó Schwartz, Jaume Veciana, Santi Sala, Miriam Royo, Alba Córdoba, Dganit Danino, Jan Skov Pedersen, Elisabet González-Mira, Ibane Abasolo, and Nora Ventosa. Impact of Chemical Composition on the Nanostructure and Biological Activity of α-Galactosidase-Loaded Nanovesicles for Fabry Disease Treatment, ACS Appl. Mater. Interfaces 2021, 13, 7, 7825–7838 ( https://doi.org/10.1021/acsami.0c16871).

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Multivalent self-assembled platforms for the delivery of chemotherapeutic drugs

Twenty years ago, the 4 February was declared World Cancer Day with the global challenge of cancer would not be forgotten. Since then, huge progress has been made to understand, prevent, diagnose, and treat cancer.

NANBIOSIS as an ICTS (Singular Scientific and Technical infrastructures) for biomedical research plays a very important role in the fight against cancer.

Dr. Miriam Royo, who leads NANBIOSIS unit 3 of Synthesis of Peptide, explains one of the projects in which the ICTS is involved in relation with cancer therapy.

The improvement of solubility and stability of clinically approved chemotherapeutic drugs still represent a big challenge in cancer therapy. In fact, many of these drugs have low water solubility, which forces to administer larger volume doses to achieve the desired biological effect, and increases the side effects suffered from patients. The active principle can be chemically modified to increase the solubility, and administered as prodrug which, however, has to be enzymatically metabolized to have therapeutic effect and only a low percentage of the free drug is achieved. Moreover, some of the chemotherapeutic drugs are unstable at physiological conditions due to their chemical structure, and rapidly degrades before reaching the tumor tissue, further reducing the effectiveness of the treatment. Drugs commonly used in clinical chemotherapy treatments for advanced colorectal cancer and triple negative breast cancer, such as SN38, 5-fluorouracil (5-FU) and paclitaxel (PTX), have presented these problems, which affect their efficacy and tolerance to treatment by patients.

Drug delivery nanosystems based on biocompatible polyethylene glycol (PEG)-based multivalent platforms conjugated to hydrophobic drugs (SN38, PTX among others) are developed by the Multivalent Systems for Nanomedicine (MS4N) goup of Centro de Investigación Biom´dcia en Red (CIBER-BBN) at the Institute for Advanced Chemistry of Catalonia (IQAC-CSIC). The resulting water-soluble conjugates have also the ability to self-assemble in aqueous media in nanoscale micellar structures improving the pharmacokinetic profile of drugs. In these systems, the intact active principle can be released in a controlled manner thanks to the presence of degradable bonds, between the drug and the polymer, which are sensitive to chemical or biological stimuli, favoring its accumulation in tumor.

Systems containing only one drug (SN38 or PTX) for monotherapy and two different drugs (as SN38 and 5-FU) for combined therapy treatments are developed to improve the therapeutic efficacy of the free drugs and decrease their secondary effects.  The multivalence nature of these systems also allows the possibility to add targeting agents, such as tumor specific peptide ligands thus increasing the specificity of the platforms towards the cancer cells. These peptide ligands have been produced at the Synthesis of Peptides Unit (U3) of NANBIOSIS.

This project (RTI2018-093831-B-I00) is funded by MICIN/AEI/10.13039/501100011033 and by “ERDF A way to of making Europe and performed in collaboration with Dr. Ibane Abasolo group of CIBER-BBN at Vall d’Hebron Research Institute (VHIR) and the In Vivo Experimental Platform (U20) of NANBIOSIS under the frame of CIBER BBN intramural collaborative projects (PolyPlaTher, Colocomb and Nanomets).

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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 DELOSTM 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

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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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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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Researchers of NANBIOSIS U3 working in a project to develop molecules with neutralizing properties of SARS-CoV-2

The research group of Chemical Multivalent Systems for Nanomedicine and NANBIOSIS U3 Sinthesys of Peptides Unit, of IQAC-CSIC and CIBER-BBN, participates in a new project that seeks to develop molecules with neutralizing properties of SARS-CoV-2, the cause of the COVID-19 disease, for the treatment of patients requiring hospitalization and clinical supervision due to the severity of the infection.

The project, led by the Public University of Navarra (UPNA) and Navarrabiomed, counts with the participation of researchers from institute of advanced chemistry of catalonia (Institute of Advanced Chemistry of Catalonia), IRB Barcelona (Institute for Biomedical Research), CIBER-BBN (Center for Networked Biomedical Research in the thematic area of Bioengineering, Biomaterials and Nanomedicine) and the IRTA (Institute of Agrifood Research and Technology).

With an expected duration of twelve months, the project brings together a multidisciplinary team: chemical synthesis, protein engineering, structural analysis, cell biology, as well as specialists in BSL3 biosafety conditions (the third level of biosafety for laboratories of a scale of four) to be able to test the potential of these molecules.

These molecules with neutralizing properties of SARS-CoV-2 are based on specific peptides of the ACE-2 receptor capable of reducing or nullifying the infectivity of SARS-CoV-2. The chemical part of the project will be carried out by Miriam Royo and Daniel Pulido (NANBIOSIS Unit 3), with the design and performance of the synthesis of ligands based on the ACE-2 receptor.

The consortium partners hope that “the availability of molecules with high inhibitory efficacy will help substantially to mitigate the socioeconomic impact of the pandemic, due to the persistence and / or future outbreaks of SARS-CoV-2 or other potentially dangerous coronaviruses and routes of similar entry ”, in the words of Jacinto López Sagaseta (Navarrabiomed).

The project has been granted in the “Overcome Covid-19 Fund”. This inicitative was created by Crue Spanish Universities, CSIC and Banco Santander with 8.5 million to bust three strategic axes against covid-19: applied research on the virus and its prevention, social impact and strengthening the technological capacity of the universities, and reducing the digital gap. euros. 35 proposals were have been selected out of the 700 submitted.

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