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New fluorescent nanovesicles for intracellular biomarker detection

A new work by researchers from the CIBER-BBN at the Barcelona Institute of Materials Science ICMAB-CSIC, together with a team from the University of Rome Tor Vergata, presents new nanovesicles capable of crossing biological barriers such as cell membranes, maintaining their sensory capacity, making them attractive probes for intracellular biomarker detection.

“The development of probes capable of detecting the biological environment and signaling the presence of a specific target molecule is a challenge with relevance in a variety of biomedical applications, from drug administration to diagnostic tools” says Mariana Köber, one of those responsible of the investigation together with Nora Ventosa and Alessandro Porchetta from the University of Rome Tor Vergata.

In this work, which has been published in Advanced Functional Materials, the design of functionalized fluorescent nanovesicles with biomimetic DNA capable of translating their binding with a target molecule into an optical output is presented, through a change in the transfer of resonance energy. Förster (FRET) and fluorescent emission. These Quatsomes (QS) nanovesicles are an emerging class of highly stable small unilamellar vesicles ≈50–100 nm in diameter, formed by the self-assembly of ionic surfactants and sterols in aqueous media. Their high stability, also in body fluids, unilaminarity and particle-to-particle homogeneity make them an attractive soft material for detection applications. “QS nanovesicles are loaded with fluorescent waves based on amphiphilic nucleic acids to produce programmable FRET active nanovesicles that function as highly sensitive signal transducers,” she explains.

The CIBER-BBN researchers have participated in the characterization of the photophysical properties of these nanovesicles and the highly selective detection of clinically relevant microRNAs with sensitivity in the nanomolar range has been demonstrated. This production of nanovesicles and their physicochemical characterization has been carried out thanks to the services of ICTS NANBIOSIS, through its unit 6 of Biomaterials Processing and Nanostructuring at the ICMAB-CSIC.

According to the authors, the proposed strategy could easily be adapted to the detection of different biomarkers: “we hope to achieve a bioimaging platform for the detection of a wide range of nucleic acids and other clinically relevant molecules in body fluids or directly in cells, thanks to the ability of Quatsomes for intracellular delivery. “

  • Figure: Schematic representation of the DNA-grafted QS nanovesicles. Adv Funct Materials, Volume: 31, Issue: 46, First published: 11 August 2021, DOI: (10.1002 / adfm.202103511)

Article of reference

Marianna Rossetti, Lorenzo Stella, Judit Morlà-Folch, Sara Bobone, Ariadna Boloix, Lorena Baranda, Danila Moscone, Mònica Roldán, Jaume Veciana, Miguel F. Segura, Mariana Köber… Engineering DNA-Grafted Quatsomes as Stable Nucleic Acid-Responsive Fluorescent Nanovesicles . https://doi.org/10.1002/adfm.202103511

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Nora Ventosa, president of the TECNIO Association.

Nora Ventosa, Scientific Director of NANBIOSIS Unit 6, is the president of the new Association of TECNIO. the association to promote technology transfer to Catalonia that was established on November 8, 2021 with the collaboration of all Catalan universities, the I-CERCA foundation and the CSIC.

This association promotes technology transfer to companies through the connection of research groups with TECNIO, as it is the case of the DBA. An initiative that includes the support of the Generalitat per mitjà d’ACCIÓ, the agency for the competitiveness of the company of the Departament d’Empresa i Treball.

The new Associació TECNIO is made up of 59 research groups that currently hold the TECNIO accreditation granted by ACCIÓ, a seal that identifies technology developers in Catalonia to facilitate the connection between the companies.

The objective of this new entity is to group and make visible the activity of the research groups within the TECNIO sector, encourage collaboration and promote them as an instrument of connection between the business sector and the administration. As part of the Autonomous University of Barcelona, ​​the University of Barcelona, ​​the University of Girona, the University of Lleida, the Polytechnic University of Catalonia, the Pompeu Fabra University, the Ramon Llull University, the Rovira i Virgili University, the University of Vic , the I-CERCA foundation and the CSIC with the aim of accelerating the transfer of knowledge from the research laboratory environment to society.

At the presentation ceremony of the new association, which took place at the Autonomous University of Barcelona (UAB), participated the Minister of Business and Employment, Roger Torrent i Ramió; the Regional Minister for Research and Universities, Gemma Geis; the General Director of Industry and CEO of ACCIÓ, Natàlia Mas; the general director of Innovation and Entrepreneurship, Lluís Juncà; the rector of the UAB, Javier Lafuente; and the president of the TECNIO Association, Nora Ventosa.

Source of information:

https://govern.cat/salapremsa/notes-premsa/415363/crea-lassociacio-tecnio-impulsar-transferencia-tecnologica-catalunya

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‘SAFE-N-MEDTECH’ and ‘PHOEHIX’ OITBs in CIBER-BBN and NANBIOSIS annual Conference.

National and international leading researchers met online last November 15 and 16 at the XV CIBER-BBN Annual Congress to discuss the latest advances in bioengineering, biomaterials and nanomedicine research, and promote further collaborations in the field.

This year’s CIBER-BBN Annual Conference included three plenary lectures given by internationally recognized experts in the fields of SARS-CoV-2 infection and vaccination, biomedical signal processing for sleep disorders, and regenerative medicine and biosensors. In addition to a selection of internal collaborations, valorization projects and collaboration projects with the CIBER of Oncology, the three programs of the Precision Medicine Infrastructure (IMPaCT) were presented.

NANBIOSIS ICTS contributed to the scientific program of the Conference with a session dedicated to the Open Innovation Test Beds (OITBs). More precisely, Dr. Ángel del Pozo, from Biokeralty presented the SAFE-N-MEDTECH OITB as an example of innovation booster for medical devices, while Dr. Emre Türeli, from MyBiotech GmbH, was invited to describe PHOENIX, a Pharmaceutical OITB for Enabling Nano-pharmaceutical Innovative Products.

Both OITBs’ scope is to cover the gap between research in nanomedicine and clinical practice. Their main objective is to provide the research community and the rest of stakeholders with a fully functional infrastructure for the testing, validation and upscaling of new nano-pharmaceuticals and medical devices through a single entry point.

NANBIOSIS is participating in SAFE-N-MEDTECH leading the corner stone work-package of preclinical validation of nano-enabled medical technologies and also contributing to their previous physico-chemical characterization. Besides that, it coordinates a Test Case about innovative nanostructured implants for bone repair, and participates in three more, all proposed by industrial partners of the project.

CIBER-BBN is participating in Phoenix OITB, as well, with the Unit 6 of NANBIOSIS ICTS (Biomaterials Processing and Nanostructuring Unit) at the Institute of Materials Science in Barcelona (ICMAB-CSIC) as well as the BioNanoSurf group at the Aragon Institute of Materials Science (INMA-CSIC).

These projects have received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreements No. 814607 (SAFE-N-MEDTECH) and No. 953183 (PHOENIX)

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NANBIOSIS U6 opens its doors to students of Nanoscience and Nanotechnology Degree at UAB

NANBIOSIS U6, Biomaterial Processing and Nanostructuring Unit from CIBER-BBN and ICMAB-CSIC, has received today the visit of students of the 4th year degree in Nanoscience and Nanotechnology of the Auonomous University of Barcelona.

During this visit, the students had the opportunity to get known of the facilities of Unit 6 of NANBIOSIS ICTS and the to work in a research laboratory. José Amable Bernabé has, Technical Coordinator of the unit, has shown the students the equipment for processing materials with compressed fluids and also some equipment for the characterization of particulate materials.

In the Degree in Nanoscience and Nanotechnology at the UAB, students prepare to synthesize, characterize and study the properties of materials at the nanoscale; to manipulate instruments and materials of test laboratories for the study of phenomena at the nanoscale and to interpret the data obtained through experimental measurements.

Unit 6 at ICMAB-CSIC is focussec on the development, characterization, and large-scale production of molecular biomaterials of therapeutic or biomedical interest, with controlled micro-, nano- and supramolecular structure. It is part of the Unique Scientific and Technical Infracstructure “NANBIOSIS”

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Radical Dendrimers as Contrast Agents for Magnetic Resonance Imaging

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

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

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

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

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Study of new liposomes for the delivery of enzymes through biological membranes

Judit Tomsen, researcher at Nanomol Group – NANBIOSIS U6 (ICMAB-CSIC and CIBER-BBN)  will defend her PhD thesis on Thursday, 15 July 2021, at 11 am in an hybrid session, from the ICMAB Seminar Room “Carles Miravitlles”. 

Further information and Registration to attend the PhD Thesis defense via Zoom  at ICMAB-website.

Supervisors:

Nora Ventosa (Scientific Director of NANBIOSIS U6 Biomaterial Processing and Nanostructuring Unit and leader of Nanomol Group of CIBER-BBN- ICMAB-CSIC

Elisabet González, Nanomol Group of CIBER-BBN – ICMAB-CSIC

Abstract: Liposomes are lipid-based nanovesicles widely explored as nanocarriers for the transport of biomolecules or drugs of interest to the place of action, and for the development of new nanomedicines. This Thesis is devoted to the study of liposomal systems functionalized with targeting-ligands, with the final goal to be used as nanocarriers of therapeutically active enzymes. The new liposomal formulations have been specifically investigated and developed for the effective transportation of α-galactosidase A enzyme through cellular and blood-brain membranes, and for the achievement of a new liposomal intravenous pharmaceutical product candidate (nanoGLA) for the treatment of Fabry disease. The achieved results support the strong potential of targeted liposomal systems for drug delivery application. The successful development and optimization of the nanoGLA product for improving the current enzymatic replacement therapy in Fabry disease especially contributes as an example of translational and interdisciplinary research.

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Jaume Veciana awarded by the Catalan Society of Chemistry with the Prize to the Scientific Excellence

Jaume Veciana Miró, Director of NANBIOSIS, has been awarded by the Catalan Society of Chemistry in its 2021 edition of Awards in research, education and dissemination with the Prize to the Scientific Excellence for his scientific career.

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New Nanomedicines for the topical treatment of complex wounds

Acute and chronic wounds are a growing global health problem. The incidence of non-healing chronic wounds has exponentially increased with the aging of the population and chronic diseases. It has been estimated that there is a 2% prevalence of chronic wounds in the general population, which is associated with an annual estimated cost of more than US$50 billion. Biomaterial-based treatments are helpful in improving small-sized and uncomplicated ulcers. Biologic molecules, named epidermal growth factors (EGFs) have demonstrated potent therapeutic efficacy along with limited side effects, however, exogenous EGF is rapidly cleared from the topical application site.

Jaume Veciana, Nora Ventosa and co-workers have reported a soft, reliable, and scalable method based on compressed CO2 for obtaining nanoconjugates of recombinant human epidermal growth factors and nanovesicles. These nanoconjugates exhibit appropriate physicochemical properties together with an antimicrobial activity preventing infections that promote complete closure of complex wounds. Therefore, such nanoconjugates are a potential nanomedicine for the topical treatment of complex wounds, particularly diabetic foot ulcers. The article published by the medical journal Advances in Therapy was chosen to be the cover of number 6 in June.

“The use of NANBIOSIS Unit 6 of Biomaterial Processing and Nanostructuring Unit (from CIBER-BBN and ICMAB-CSIC) has allowed the obtaining of various versions of the nanoconjugates as well as their physical-chemical characteristics” – explained prof. Jaume Veciana

Article of reference: Nanoconjugates: Lidia Ferrer-Tasies, Hector Santana, Ingrid Cabrera-Puig, Elisabet González-Mira, Lídia Ballell-Hosa, Carla Castellar-Álvarez, Alba Córdoba, Josep Merlo-Mas, Haydee Gerónimo, Glay Chinea, Viviana Falcón, Evelyn Moreno-Calvo, Jan Skov Pedersen, Jessica Romero, Claudia Navarro-Requena, Calixto Valdés, Miladys Limonta, Jorge Berlanga, Santiago Sala, Eduardo Martínez, Jaume Veciana and Nora Ventosa, Recombinant Human Epidermal Growth Factor/Quatsome Nanoconjugates: A Robust Topical Delivery System for Complex Wound Healing.  Adv. Therap. 2021 14 June, 2000260 [DOI]

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A new european infrastructure will facilitate the transfer of nano-pharmaceuticals from the lab to the clinic

Launch of the cross-european PHOENIX project, which will provide a new infrastructure available to research laboratories, SMEs and start-ups to facilitate the transfer of nano-pharmaceuticals from the laboratory to clinical practice. PHOENIX will have a duration of 4 years and a total budget of 14.45 million euros. Two CSIC Institutes, ICMAB (CSIC) and INMA (CSIC-UNIZAR), and one CSIC spin-off, Nanomol Technologies, participate in the project, will count with the expertise of NANBIOSIS unit 6 (from CIBER-BBN and ICMAB-CSIC), led by Nora Ventosa.

PHOENIX is an innovation project funded by EU’s Horizon2020 Framework Programme aimed to provide services for the development, characterization, testing, safety assessment, scale-up, good-manufacturing-practice (GMPs) production and commercialization of nano-pharmaceuticals from the lab to the market, making them available to SMEs, startups, research laboratories and interested users.

A total of 11 partners from academia and industry located all across Europe have joined forces to create this “Open Innovation Test Bed” for nano-pharmaceuticals. Two CSIC institutes participate in this initiative: the Institute of Nanoscience and Materials of Aragón (INMA, CSIC-UNIZAR) and the Institute of Materials Science of Barcelona (ICMAB, CSIC), both groups members of the CIBER-BBN. Nanomol Technologies S.L., a growing SME spin-off from ICMAB-CSIC, is also partner of the project.

PHOENIX, which is coordinated by Luxembourg Institute of Science and Technology (LIST), supported by the german SME MyBiotech in scientific coordination, will have a duration of 48 months starting on 1 March 2021 with a total budget of €14.45 million and a requested EU contribution of €11.1 million.

Open Innovation Test Bed for nano-pharmaceuticals

Nano-pharmaceuticals are drugs that use nanotechnology (the use of matter on an atomic, molecular, and supramolecular scale for industrial purposes) in some form to achieve enhanced drug products. For example, contrast agents are used in the form of nanoparticles rather than a molecule because nanoparticles are more stable and can stay longer in blood. Another example could be that a nanoparticle is used as a nanocarrier to encapsulate the drug substance and protect it while enhancing adsorption and biodistribution, or to target the drug to specific tissues or organs.

Nano-pharmaceuticals have the potential to drive the scientific and technological uplift, offering great clinical and socioeconomic benefits to society in general, industry, and patients. Nevertheless, affordable and advanced testing, manufacturing facilities and services for novel nano-pharmaceuticals are main prerequisites for successful implementation of these advances to further enhance the growth and innovation capacity.

The establishment of current good manufacturing practices (GMPs) in nano-pharmaceutical production on a large scale is the key step to successfully transferring nano-pharmaceuticals from bench to bedside (from the lab to the patients). Due to the lack of resources to implement GMP manufacturing on site, the upscaling and production of innovative nano-pharmaceuticals is still challenging to the main players of EU nanomedicine market, start-ups and SMEs. To allow a successful implementation of nano-pharmaceuticals in the nanomedicine field, there is an urgent need to establish a science and regulatory-based Open Innovation Test Bed (OITB).

PHOENIX: key project in taking nano-pharmaceuticals from bench to bedside

The PHOENIX project aims to enable the seamless, timely and cost-friendly transfer of nano-pharmaceuticals from lab bench to clinical trials by providing the necessary advanced, affordable and easily accessible PHOENIX-OITB which will offer a consolidated network of facilities, technologies, services and expertise for all the technology transfer aspects from characterisation, testing, verification up to scale up, GMP compliant manufacturing and regulatory guidance.

PHOENIX-OITB will develop and establish new facilities and upgrade existing ones to make them available to SMEs, starts-up and research laboratories for scale-up, GMP production and testing of nano-pharmaceuticals, either based on small chemical molecules or biologicals The services and expertise provided by the OITB will include production and characterisation under GMP conditions, safety evaluation, regulatory compliance and commercialisation boost.

“Our goal is to create a new infrastructure at European level available for all research centres and laboratories, SMEs and start-ups, to facilitate the transfer of nano-pharmaceuticals from the lab to the clinical practice” explains Jesús Martínez de la Fuente, INMA-CSIC-UNIZAR researcher.

“The role of INMA and ICMAB is to generate new services, open to the public, to characterize nano-pharmaceuticals in rder to ensure their quality” affirms Nora Ventosa, ICMAB-CSIC/CIBER-BBN researcher and Director of NANBIOSIS unit 6 Biomaterial Processing and Nanostructuring Unit.

Project partners

The 11 partners that form the PHOENIX consortium are the Luxembourg Institute of Science and Technology (LIST, Luxembourg), MyBiotech (SME from Germany), Nanomol Technologies SL, LeanBio SL and Grace Bio SL (SMEs from Spain), Cenya Imaging B.V. (SME from The Netherlands), BioNanoNet Forschungsgesellschaft mbH (BNN, Austria), CSIC (INMA, CSIC-UNIZAR and ICMAB, CSIC), Institute for Medical Research and Occupational Health (IMROH, Croatia), Research Center Pharmaceutical Engineering GmbH (RCPE, Austria), and Topas Therapeutics GmbH (Germany).

More information:

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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

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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