News U6

New edition of the course on characterization and preparation of particulate materials.

ICMAB-CSIC October 19th 2022

Amable Bernabé, from Nanbiosis U6 Biomaterial Processing and Nanostructuring Unit hosted from Monday, 3 October, to Wednesday, 5 October a course on “Characterization techniques for particulate materials”. The course counted with 10 participants from different CSIC centers.

The course was an introduction to different techniques to characterize nanoparticles and other particulate matter, including the basic fundamentals of these techniques, sample preparation, practical examples and results interpretation. It is the fifth edition of the course, which started in 2018. Amable Bernabé, technician from the Soft Materials Service, prepares and offers this course to all the CSIC community, so everyone who needs it can learn new methods to characterize nanoparticles, the theory behind the techniques, and how to manage the lab equipment devoted to these techniques. The course is offered every year through the CSIC training courses offered every year for all its staff. This year, the 10 participants were from CSIC centers of the Barcelona area: IMB-CNM, IDAEA, ICM and ICMAB, mainly.

Soft Materials Service – NANBIOSIS ICTS U6

The Soft Materials Service constitute the unit 6 of NANBIOSIS, the integrated infrastructure for the production and characterization of nanomaterials, biomaterials and systems in biomedicine, which has been recognized by Spanish Government as Unique Scientific-Technological Infrastructure (ICTS).

The Unit of NANBIOSIS provides equipment and technical assistance for the preparation and characterization of micro-and nanostructured soft molecular materials (molecular surfaces, micro- and nanoparticulate molecular materials, plastic films, dispersed systems, SAMs, etc..) with interest in different areas of application (biomedicine, electronics, energy storage and other chemical and material application areas).

The Soft Materials Service, with Amable Bernabé and David Piña as technicians, participate in many European projects and give service to the whole ICMAB community, apart from the Nanomol Research Unit, and also to other CSIC centers and research institutions and companies. In 2021, for example, 30 % of the users were external. Of these users, 14.3 % were from private companies, 58.9 % came from other research centers or universities, and 26.8 % from other ICMAB research units.

This last April 2022, the Service Materials Service, which is part of Unit6 of the ICTS Nanbiosis and CIBER-BBN, obtained the ISO 9001:2015 Quality Certification, which ensures the quality of the service provided and helps to continue with its improvement and extension to future services.

Contents of the course

Theory:

Dynamic Light Scattering (DLS) with Zetasizer Nano ZS (Malvern Instruments)
- Size distribution
- Z Potential
Nanoparticle Tracking Analysis (NTA) with Nanosight NS300 (Malvern Instruments)
- Size distribution
- Particle concentration
- Fluorescence
Light Scattering (LS) with Mastersizer 2000 (Malvern Instruments)
- Size distribution

Practice:

Sample analysis and practical cases of Dynamic Light Scattering with the Zetasizer Nano ZS (Malvern Instruments) equipment.
Samples analysis and practical cases of the Nanoparticle Tracking Analysis (NTA) technique with the Nanosight NS300 (Malvern Instruments) equipment.
Sample analysis and practical cases of the Light Scattering (LS) technique with the Mastersizer 2000 (Malvern Instruments) instrument.

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The first TECNIO Conference and NANBIOSIS’ researchers participation

More than 200 people attended the first edition of the TECNIO Conference that took place on October 19th, 2022 in Girona. Outstanding experts from research groups, companies and the Catalan administration discussed the model of technological sovereignty that Catalonia needs to generate high-impact innovation.

As far as Nora Ventosa, President of the TECNIO Association and Scientific Director of NANBIOSIS U6 Biomaterial Processing and Nanostructuring Unit (from CIBER-BBN and IQAC): “Political management is the key to ensure that the path of transference follows a high speed train”

Researchers of NANBIOSIS U2 Custom Antibody Service (CAbS) – Nb4D Group from CIBER-BBN and IQAC-CSIC presented their technological offer in the 1st TECNIO Congress

During the congress there were different presentations, round tables and an exhibition space to interact with the TECNIO agents.

For further informatio: https://www.eventbrite.es/e/tecnio-congress-2022-tickets-415838312587

Related News

Nora Ventosa, president of the TECNIO Association.

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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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Metal-free contrast agents: novel approaches

The joint expertise of CIBER-BBN Nanomol Group – NANBIOSIS U6 from at ICMAB-CSIC (José Vidal and Vega Lloveras) and NANBIOSIS U25 at UAB (Ana Paula Candiota), led to a recently published article in the prestigious journal Biomacromolecules

Brain tumours such as Glioblastomas are a challenge in the clinics and proper diagnosis and follow-up are crucial for patient outcome. Contrast agents are usually administered to patients for assessing blood brain barrier integrity and quantitation of enhancing areas are part of the clinical criteria for estimating response/relapse. However, most contrast agents currently used in clinics are based in metal elements such as Gadolinium and are not exempt of risks. In addition, due to the renal excretion route, administering such agents to some patients is contraindicated. Our work explored the potential of organic radicals anchored to dendrimers to act as contrast agents for glioblastoma studies, proposing a metal-free alternative for contrast enhanced glioblastoma studies. The article describes details of synthesis and characterization of these agents, as well as in vivo, ex vivo and in vivo magnetic resonance studies. The orthotopic immunocompetent GL261 glioblastoma murine model was used for in vivo and ex vivo studies. The novel contrast agent proved to be non-harmful for wild type mice and produced sustained and long lasting contrast in tumour-bearing mice, even in much lower doses in comparison with gadolinium administration.

The diagnosis and follow-up of high-grade brain tumours such as glioblastomas relies mostly in MRI, and contrast agents currently used are based on Gadolinium, which is not exempt of risks. The resarchers’ approach explores organic radicals anchored to dendrimers as a metal-free alternative to produce contrast enhancement in MRI, safer than Gadolinium-based compounds, and with translational potential.

Article of reference:
Zhang S, Lloveras V, Lope-Piedrafita S, Calero-Pérez P, Wu S, Candiota AP, Vidal-Gancedo J. Metal-Free Radical Dendrimers as MRI Contrast Agents fof Glioblastoma Diagnosis: Ex Vivo and In Vivo Approaches. Biomacromolecules. 2022 Jun 24. doi: 10.1021/acs.biomac.2c00088.

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Nora Ventosa appointed Research Professor under the Materials Science

Nora Ventosa, the Scientific Director of NANBIOSIS U6 of Biomaterial Processing and Nanostructuring Unit (and IP of the NANOMOL Group of CIBERBBN at ICMAB-CSIC) has been appointed Research Professor in the last call of the Spanish National Reserach Council (CSIC)

This elective process for the selection and appointment of career civil servant, by internal promotion, in the Scale of Research Professors of Public Research Organisms had oppen 6 new positions for Professors under the Materials Science.

Nora Ventosa is a Chemical Engineer by the Institut Químic de Sarrià (IQS) and Doctor in Chemistry by the Universitat Ramon Llull. Her research is focused on green chemistry, soft materials and nanobiochemistry. She is devoted to develop and apply new methodologies, based on compressed fluids, in order to gain control of molecular self-assembly in solution.

Prof. Ventosa is also co-founder of the spin-off Nanomol Technologies, vicepresident of the Societat Catalana de Química (SCQ-IEC), member of the Administration Council of ACCIÓ, the Catalan Government agency for the promotion of the competitiveness within companies, and President of the TECNIO Research Association. She has participated, organized and directed more than 50 research projects, funded by different national and international agencies, public, private and industrial, including the European projects Smart4Fabry (Smart multifunctional GLA-nanoformulation for Fabry disease) or Phoenix (Open Innovation Test Bed for Enabling Pharmaceutical Innovative Products).

U6: Biomaterials processing and Nanostructuring unit

Unit 6 of NANBIOSIS, on Biomaterials processing and Nanostructuring unit from CIBER-BBN, hosted at ICMAB-CSIC, with Scientific Director Nora Ventosa, from the Nanomol-Bio research group. The U6 gathers several laboratories, perfectly equipped, to perform the mission of this facility: the development, characterization, and large-scale production of molecular biomaterials of therapeutic or biomedical interest, with controlled micro-, nano- and supramolecular structure. One example of Key-Enabling-Technology (KET) available in this unit in collaboration with the SME Nanomol Technologies (spin off of CSIC) is a simple and green one-step methodology, DELOS, based on the use of compressed fluids (CF), such as CO_2, to prepare particulate materials with precise and reproducible structural characteristics at micro-, nano- and supramolecular levels (size, shape, internal structural gradients, supramolecular organization and crystalline purity). This example shows one of the singularities of this unit is that counts with CF–based plants at different scales, from mL to L, which allow process development by QbD and process scale-up. Recently U6 NANBIOSIS, together with the Soft Scientific and Technical Service, was accredited with the ISO9001 certification for the standard quality control system.

Congratulations Nora!

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ISO 9001:2015 Quality Certification for the Soft Scientific and Technical Service at ICMAB and Unit

The aim of the quality certification obtained is to ensure the quality of the service provided and to continue with its improvement and extension to future services.

The Scientific and Technical Service for the characterization of nano and biomaterials, the Soft Lab, run by the Nanomol Research Unit of the Institute of Materials Science of Barcelona (ICMAB, CSIC), and which is part of Unit 6 of the ICTS Nanbiosis, and CIBER-BBN, aims to offer characterization services of micro- and nanostructured soft molecular materials to the entire scientific community that requires them.

To this end, the Soft technical service has several laboratories at ICMAB equipped for the study of the stability of solutions, the study of particle size distribution, the determination of the density of porous solids, or the study of biomolecular interactions of materials, among others.

Following a series of audits that evaluated the Soft service’s characterization services, the service was awarded the ISO 9001:2015 quality certification at the end of 2021.

The ISO standard is the most widespread and recognised reference system for the implementation and certification of a quality management system, based on three axes: continuous improvement, customer satisfaction and involvement of all stakeholders.

The principles of quality management taken into account in the evaluation are: focus on the customers; management leadership; commitment with the people; process approach; continuous improvement; evidence-based decision making; relationship management.

Therefore, the Soft service is responsible, as reflected in the quality commitment agreement, for providing its services with the highest quality standards, and for the continuous monitoring of various indicators to assess the degree of compliance with the quality commitments, including the customer satisfaction degree. These statistics will be part of the corresponding quality reports and reviewed by the management team, as set out in the Soft/U6 Nanbiosis quality policy.

Congratulations to the Soft service and to all the Nanomol team for achieving this quality certification!

Soft Service ICMAB / U6 Nanbiosis

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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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Stable nanovesicles for the delivery of microRNA in cancer treatment

Nanovesicles, known as quatsomes, have been successfully engineered to encapsulate and deliver microRNAs for the treatment of tumors.
These nanovesicles are produced by a simple GMP compliant process, an unavoidable requirement for the clinical use of new drug candidates.
The study, published in Small, has been highlighted in the Women in Materials Science issue of Advanced Materials.

“The beauty of these quatsomes nanovesicles is that they can be easily engineered for the delivery of a variety of nucleic acids. Importantly, they are stable at room temperature, which avoids problems associated to cold chain requirements”, says Nora Ventosa, Scientific Director of NANBIOSIS U6.

MicroRNAs (also known as miRNAs) are small RNA molecules that can interfere with the stability of other RNA molecules (specifically, messenger RNA). They have many potential therapeutic uses due to the central role they play in major diseases. However, these molecules are still infrequently used in patients due to their instability in the bloodstream and their poor ability to reach specific tissues. A potential strategy to improve the clinical delivery of miRNAs in the body is to encapsulate them in tiny carriers that compensate its current shortcomings, without side effects and offering other complementary functions.

To this end, researchers have developed and designed especially for this application nanostructures, known as quatsomes, composed by two closed lipid layers. In a new publication in Small, which is highlighted in the “Women in Materials Science” Issue of Advanced Materials, researchers present a newly engineered formulation of quatsomes that have a controlled structure, composition and pH sensitiveness.

The study is the result of an interdisciplinary team of researchers from the Institute of Materials Science of Barcelona, ICMAB-CSIC, the Vall d’Hebron Research Institute (VHIR)-UAB, the Institute for Bioengineering of Catalonia (IBEC), the Barcelona Institute of Science and Technology (BIST), the CIBER network on Bioengineering, Biomaterails and Nanomedicine (CIBER-BBN), the company Nanomol Technologies SL, the Technion-Israel Institute of Technology and the Institute for Complex Molecular Systems (ICMS).

“In this study we have collaborated with hospitals, research networks and companies. The successful results obtained illustrate the importance of collaboration across fields and beyond the academic system” says Ventosa.

These new quatsomes can be coupled with the miRNA and injected intravenously into the body to be delivered in neuroblastoma primary tumors or in frequent sites of metastasis, such as the liver or lung, with a higher success and stability than if the miRNA were injected by itself. Once delivered, the miRNA has an effect on the cell proliferation and survival-related gens in the tumors, decreasing the tumor’s growth rate.

Many properties make quatsomes a good fit for these applications: they are less than 150 nm in size and are stable in a liquid solution for more than 6 months; they also have tunable pH sensitiveness, which means that different pH levels around can trigger different responses.

Quatsome production and their physicochemical characterization has been performed by the ICTS “NANBIOSIS,” more specifically in the Biomaterial Processing and Nanostructuring Unit (U6), Unit of the CIBER in Bioengineering, Biomaterials & Nanomedicne (CIBER-BBN) located at the Institute of Materials Science of Barcelona (ICMAB-CSIC) and led by Nora Ventosa

The production of these nanovesicles has been optimized with their final application in mind and to make sure they can be used in clinics. Through a green and scalable one-step process, named DELOS, researchers have designed a procedure that is fully compliant with Good Manufacturing Practice (GMP) guidelines stablished by the European Union. “It is time to translate our scientific findings for the benefit of patients” says Ariadna Boloix, VHIR researcher.

The development of miRNA delivery systems containing an active targeting for neuroblastoma is performed under the frame of a CIBER-BBN valorization project “Targeted Quatsome nanocarriers for the delivery of microRNA for neuroblastoma therapy” (TAG-SMARTLY), coordinated by the Nanomol group in collaboration with the Multivalent Systems for Nanomedicine (MS4N) group of the CIBER-BBN at IQAC-CSIC and the Synthesis of Peptides Unit of Nanbiosis (U3).

In this publication, the functionality of quatsomes in delivering miRNAs is demonstrated with a specific extracranial solid tumor common in pediatric cases of cancer known as neuroblastoma, which is responsible for roughly 15 % of all pediatric cancer deaths and lacks therapies for high-risk patients. The results show that quatsomes protect the miRNA from degradation and increase its presence on liver, lung and xenografted neuroblastoma tumors, amongst other tissues.

Reference article:

Engineering pH-Sensitive Stable Nanovesicles for Delivery of MicroRNA Therapeutics Ariadna Boloix, Natalia Feiner-Gracia, Mariana Köber, Javier Repetto, Rosa Pascarella, Aroa Soriano, Marc Masanas, Nathaly Segovia, Guillem Vargas-Nadal, Josep Merlo-Mas, Dganit Danino, Inbal Abutbul-Ionita, Laia Foradada, Josep Roma, Alba Córdoba, Santi Sala, Josep Sánchez de Toledo, Soledad Gallego, Jaume Veciana, Lorenzo Albertazzi, Miguel F. Segura*, Nora Ventosa* Small, 18, 3, 2022 DOI: 10.1002/smll.202101959

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Submissions open for Special Issue of MDPI on Fluorescent Organic Nanoparticles for Bioimaging and Theragnostics

Nora Ventosa and Mariana Köber, from NANBIOSIS Unit 6 of CIBER-BBN and ICMAB-CSIC, and Judit Morlà-Folch, from the BioMedical Engineering and Imaging Institute at the Icahn School of Medicine at Mount Sinai, New York, are editors of the Special Issue of MDPI Pharmaceutics.

The Special Issue on “Fluorescent Organic Nanoparticles for Bioimaging and Theragnostics“ belongs to the “Nanomedicine and Nanotechnology” section and has a deadline for manuscript submissions on 25 July 2022.

The guest editors explain the main topic of this Special Edition:

“Fluorescence-based techniques play an essential role in the study of biological events in tissues and animals due to their specificity and noninvasive nature. However, realizing the whole potential of today’s fluorescence imaging and detection in terms of speed, resolution, and sensitivity, requires fluorescent labels that combine stability, a very high brightness, and a high photostability.

In this regard, novel, bright and stable organic fluorescent nanoparticles have evolved rapidly during the last few years, allowing further development of novel, experimental treatments and imaging strategies, including photodynamic therapy or image-guided surgery.

These results shine a spotlight on fluorescent nanomaterials as promising candidates for imaging and theragnostics in several health disorders. In this Special Issue, we invite authors to report on their recently developed, fluorescent, organic nanoparticles for imaging, diagnostics, and the treatment of diseases.”

If you have a relevant manuscript, you can submit it at MDPI in the submission form before 25 July 2022. All papers will be peer-reviewed, and research articles, review articles or short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website. More information on submission here.

About the Pharmaceutics MDPI Journal

“Pharmaceutics (ISSN 1999-4923) is an online open access journal on the science and technology of pharmaceutics and biopharmaceutics. The scientific community, the wider community and the general public have unlimited and free access to the content as soon as a paper is published; this open access to your research ensures your findings are shared with the widest possible audience. Please consider publishing your impressive work in this high quality journal. We would be pleased to welcome you as one of our authors.” – Editor-in-Chief Prof. Dr. Yvonne Perrie from the Strathclyde Institute of Pharmacy and Biomedical Sciences at the University of Strathclyde.

Source of information: ICMAB-CSIC

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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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