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Posts on Jan 1970

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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SAFE-NMT Open Call for development and market of innovative MedTech solutions based on nanotechnology

An Open Call within H2020 project SAFE-N-MEDTECH OITB  -Safety testing in the life cycle of nanotechnology-enabled medical technologies for health– has been launched with the objective of providing services and support to companies and other organizations with the aim of accelerating the development and commercialization of innovative MedTech solutions based on nano-enabled technology.

SAFE-N-MEDTECH  in which CIBER-BBN is a partner througth its ICTS NANBIOSIS, gathers expertise from 28 partners around the world focused in enabling the safe translation of nano-enabled medical technologies from Proof of Concept to markets and clinical practice funded project

SAFE-N-MEDTECH with its key expertise and extensive knowledge in nano-enabled medical technologies, offers characterization, pre-clinical validation, access to biobanks and patient samples, scale up and regulatory support, technology assessment and horizon scanning.

Submission deadline: March 21st 2022, 23:59 CET

CALL DOCUMENTS – HOW TO APPLY:

  • Guidelines for Applicants The Guide for Applicants contains the basic information needed to guide you in preparing a proposalfor submission to the SAFE-N-MEDTECH Open Call. It gives an introduction on how to structureyour proposal. It also describes how to submit the proposal and the evaluation criteria.
  • Application Form

EXAMPLES OF SUPPORT SERVICES:

Nanoparticle Characterisation

  • Chemical Composition
  • Physical properties
  • Drug loading/release
  • RNA quantification and integrity
  • Sterility and Toxicity

Pre-Clinical Development

  • Antibody production
  • Peptide/Protein synthesis
  • Oligonucleotide synthesis
  • Immune response monitoring
  • Cellular assays
  • Biological evaluation
  • Nanoparticle development
  • Design and optimisation of biosensor platforms
  • Access to human samples and Biobanks
  • In vivo experiments

In Silico

  • In silico modelling

Clinical Validation

  • RNA extraction
  • RNA/DNA sequencing
  • Binding affinity measurement
  • Immune response monitoring

Assistance in prototyping and qualification of manufacturing facilities

Business development coaching, links with business angels, investors, capital risk, etc

Regulatory Assessment

  • Regulatory support to Europe and US approval

Health Technology Assessment

  • First evaluation of the project/product based on Health Technology Assessment (HTA)and Healthcare system needs
  • Technology scanning to identify redundancies/synergies

This call uses funds obtained within the scope of the SAFE-N-MEDTECH project funded by European Union´s Horizon 2020 Research and Innovation Program. (Grant Agreement No. 814607)

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The integrin beta1 modulator Tirofiban prevents adipogenesis and obesity by the overexpression of integrin-linked kinase: a pre-clinical approach in vitro and in vivo

Obesity is caused by the enlargement of the white adipose tissue (WAT) depots, characterized by the hypertrophic enlargement of malfunctioning adipocytes within WAT, which increases the storage of triglycerides (TG) in the lipid droplets (LD). Adipogenesis pathways as well as the expression and activity of some extracellular matrix receptors integrins are upregulated. Integrinβ1 (INTB1) is the main isoform involved in WAT remodeling during obesity and insulin resistance-related diseases. We recently described Integrin Linked Kinase (ILK), a scafold protein recruited by INTB1, as an important mediator of WAT remodeling and insulin resistance. As the few approved drugs to fight obesity have brought long-term cardiovascular side effects and given that the consideration of INTB1 and/or ILK modulation as anti-obesogenic strategies remains unexplored, we aimed to evaluate the anti-obesogenic capacity of the clinically approved anticoagulant Tirofiban (TF), stated in preclinical studies as a cardiovascular protector.

TF reduces the levels of F‑actin in adipocytes. Deprived differentiated adipocytes from c3H10T1/2 were treated with TF 50 µM or vehicle (CT) or co‑treated with specific INTB1 blocking antibody (HMB1) for the indicated times.

In the picture: Confocal images of F-actin dyed with phalloidin (red) and nuclei with DAPI (blue) of differentiated adipocytes treated with Tirofiban or vehicle (CT), where previously Integrin-beta1 was blocked with a specific blocking antibody (HMB1) for the indicated times. Scale bars 50 μm. 

F-actin confocal images were determined by the Confocal Microscopy Service of the ICTS ‘NANBIOSIS’ U17, of the Biomedical Research Networking Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) with the technical assistance of Isabel Trabado, and pharmacokinetics were determined in the Applied Chemistry and Biotechnology Center (CQAB), both at Universidad de Alcalá.

Article of Reference: 

de Frutos S, Griera M, Hatem-Vaquero M, Campillo S, Gutiérrez-Calabres E, García-Ayuso D, Pardo M, Calleros L, Rodríguez-Puyol M, Rodríguez-Puyol D. The integrin beta1 modulator Tirofiban prevents adipogenesis and obesity by the overexpression of integrin-linked kinase: a pre-clinical approach in vitro and in vivo. Cell Biosci. 2022 Jan 28;12(1):10. doi: 10.1186/s13578-022-00746-1. PMID: 35090553.

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AWARDS of the Academy of Pharmacy of Castilla y León 2021 to researchers from NANBIOSIS U10

The leader of the NanoBioCell Group form CIBER-BBN and UPV/EHU, Jose Luis Pedraz, and the reaearches Laura Saenz del Burgo and Markel Lafuente have received the 2021 Award from the Academy of Pharmacy of Castilla y León, on February 4, at the city ​​of Salamanca, for the work entitled: “Design and Characterization of a biotin formulated with nanocellulose, alginate and Gags for use in 3D bioprinting and application in cartilage regeneration“, the content of this research work has been published in the Journal Macromolecular Science under the title: “Chondroitin and Dermatan Sulfate Bioinks for 3D Bioprinting and Cartilage RegenerationThe pharmacotechnical and rheological characterization work of the designed bioinks has been carried out in the U10 Drug Formulation of the Nanbiosis ICTS of the Faculty of Pharmacy of the University of the Basque Country and CIBER-BBN.


In addition, Prof. Jose Luis Pedraz has been appointed Corresponding Academician at the Academy of Pharmacy of Castilla y León.


Also the researcher of the NanoBiocel group, Professor Edorta Santos Vizcaíno, belonging to the CIBER BBN and the U10 Drug Formulation of the Nanbiosis ICTS, and María Gil Atienza, have been recognized that same day, with a second prize by the Academy of Pharmacy of Castilla y León for the research work: “Use of extracellular vesicles to transport antitumor agents in the treatment of cancer”. This work was carried out in the Laboratory of Pharmacy and Pharmaceutical Technology of the University of the Basque Country.

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Women in the fight against breast cancer: Ibane Ibasolo

The International Day of Women and Girls in Science on February 11 honor women’s significant achievements in science and place a much-needed focus on girls entering Science, Technology, Engineering, and Mathematics (STEM) careers.

We want to take this day to congratulate all the women scientists, especially our scientists at NANBIOSIS ICTS. Some of them take an active role in the dissemination of research results and reseach contribution to the society, as Dr. Ibane Abasolo who last week participated in different events to explain her team work in the figth against breast cancer.

Ibane Abasolo is the Scientific Coordinator of NANBIOSIS U20 and also the leader of the Drug Delivery & Targeting group of the CIBER-BBN at the Vall d’Hebron Research Institute (VHIR) which coordinates the unit 20 of NANBIOSIS, a team composed mainly by women.

The group cooworks to improve cancer treatment through the development of nanoparticles specially directed towards breast cancer stem cells. These cells are the ones that, despite dividing slowly, give rise to the differentiation of the rest of the tumor cells and are also the most resistant to conventional antitumor treatments.

That is why the group seeks to attack these cells in three ways:

i) selected drugs that induce the differentiation of tumor stem cells into more differentiated cells (and easier to treat),

2) using mechanisms to evade the efflux pumps of drugs and

3) targeting the nanoparticles specifically towards tumor stem cells by using targeting agents (ie antibodies) against antigens on the surface of tumor stem cells.

Dr. Abasolo has illustrated these three approaches by citing papers published in her group during 2021, in which the ICTS Nanbiosis U20 has also directly participated:

Gustavo Carreño, Alfredo Pereira, Fabián Ávila-Salas, Adolfo Marican, Fernanda Andrade, Maria Mercé Roca-Melendres, Oscar Valdés, Sekar Vijayakumar, Simó Schwartz, Ibane Abasolo, Diana Rafael, Esteban F. Durán-Lara, Development of “on-demand” thermo-responsive hydrogels for anti-cancer drugs sustained release: Rational design, in silico prediction and in vitro validation in colon cancer models, Materials Science and Engineering: C, Volume 131, 2021, 112483, ISSN 0928-4931, https://doi.org/10.1016/j.msec.2021.112483.

Yolanda Fernández, Julie Movellan,Laia Foradada, Vanessa Giménez, Natalia García-Aranda, Sandra Mancilla, Ana Armiñán, Sven Even Borgos, Astrid Hyldbakk, Anna Bogdanska, Oliviero L. Gobbo, Adriele Prina-Mello, Jessica Ponti, Luigi Calzolai, Oleksandr Zagorodko, Elena Gallon, Amaya Niño-Pariente, Alison Paul, Simó Schwartz Jr, Ibane Abasolo, María J. Vicent In Vivo Antitumor and Antimetastatic Efficacy of a Polyacetal-Based Paclitaxel Conjugate for Prostate Cancer Therapy. Adv Healthc Mater. 2021 Oct 27;e2101544. doi: 10.1002/adhm.202101544.

Diana Rafael, Maria Mercè Roca Melendres, Fernanda Andrade, Sara Montero, Francesc Martinez-Trucharte, Mireia Vilar-Hernandez, Esteban Francisco Durán-Lara, Simó Schwartz Jr, Ibane Abasolo,
Thermo-responsive hydrogels for cancer local therapy: Challenges and state-of-art, International Journal of Pharmaceutics, Volume 606, 2021,
120954, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2021.120954.

Marwa M Abu-Serie , Fernanda Andrade, Patricia Cámara-Sánchez, Joaquin Seras-Franzoso, Diana Rafael, Zamira V Díaz-Riascos, Petra Gener, Ibane Abasolo, Simó Schwartz Jr Pluronic F127 micelles improve the stability and enhance the anticancer stem cell efficacy of citral in breast cancer. Nanomedicine VOL. 16, NO. 17. 2021 Jul;16(17):1471-1485. doi: 10.2217/nnm-2021-0013.

Eva Espinosa-Cano, Miguel Huerta-Madroñal, Patricia Cámara-Sánchez, Joaquin Seras-Franzoso, Simo Schwartz, Ibane Abasolo, Julio San Román, Maria Rosa Aguilar, Hyaluronic acid (HA)-coated naproxen-nanoparticles selectively target breast cancer stem cells through COX-independent pathways, Materials Science and Engineering: C, Volume 124, 2021, 112024, ISSN 0928-4931, https://doi.org/10.1016/j.msec.2021.112024.

Fernanda Andrade, Diana Rafael, Mireia Vilar-Hernández, Sara Montero, Francesc Martínez-Trucharte, Joaquin Seras-Franzoso, Zamira V. Díaz-Riascos, Ana Boullosa, Natalia García-Aranda, Patricia Cámara-Sánchez, Diego Arango, Marika Nestor, Ibane Abasolo, Bruno Sarmento, Simó Schwartz, Polymeric micelles targeted against CD44v6 receptor increase niclosamide efficacy against colorectal cancer stem cells and reduce circulating tumor cells in vivo, Journal of Controlled Release, Volume 331, 2021, 198-212, ISSN 0168-3659, https://doi.org/10.1016/j.jconrel.2021.01.022.

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Women in Signal Processing: Raquel Bailón

The International Day of Women and Girls in Science on February 11 honor women’s significant achievements in science and place a much-needed focus on girls entering Science, Technology, Engineering, and Mathematics (STEM) careers. We want to take this day to congratulate all the women scientists, especially to our scientists at NANBIOSIS ICTS.

In this occasion we want to put the spotlight on Raquel Bailon, researcher of Bsicos Group coordinating NANBIOSIS Unit 27 of High-Performance Computing form CIBER-BBN and University of Zaragoza-I3A, who last month has been highlighted by Inside Signal Processing Newsletter.

In the interview Dr. Raquel Bailon talks about her motivations and aspirations when she was a child and how she chose to develop her career in the field of Signal Processing, explains her passion for biomedical signal processing research and the relevance of her work for society.

Dr. Bailon also gives wise and practical advices to young scientists/engineers in the field of signal processing. Raquel stresses the need of having a deep knowledge of the field of application, working in a multidisciplinary team and promoting collaboration and clinical translation of research, without frontiers

To access the full interview, click here

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Women Scientists in your neighborhood: Estefanía Peña

The International Day of Women and Girls in Science on February 11 honor women’s significant achievements in science and place a much-needed focus on girls entering Science, Technology, Engineering, and Mathematics (STEM) careers. We want to take this day to congratulate all the women scientists, especially to our scientists at NANBIOSIS ICTS, some of whom take an active role in the organization of events to celebrate this day, as Estefanía Peña in the initiative “Women Scientists in your neighborhood” form the University of Zaragoza.

Estefanía Peña is the Cientific Coordinator of Unit 13 of Tissue & Scaffold Characterization from the ICTS NANBIOSIS since the creation of the Unit in 2007 by the Network Biomedical Research Center in Bioengineering, Biomaterials and Nanomedicine, (CIBER-BBN) and the University of Zaragoza-I3A. Estefanía participates this year in the Campaign “I’m a Scientist, I live in your neighborhood” organised by Scientific Culture Unit of the University of Zaragoza to break stereotypes that present the women scientists as heroines, geeks or with little social life, while the scientists who live in our neighborhoods show the reality of a vibrant and exciting career choice, to vindicate the role of women in science, break the gender gap and offer close references to girls and adolescents.

“My name is Estefanía Peña and I am Professor of Mechanics of Continuous Media and Theory of Structures at the School of Engineering and Architecture. In addition to teaching, I am dedicated to research in the field of Biomedical Engineering at the Engineering Research Institute of Aragon (I3A).

I am delighted to share with you the story of why I ended up being a scientist and dedicated myself to research in Engineering applied to Life Sciences. I was born in Zaragoza and have lived in Zaragoza practically all my life, except for a few short periods in France and England. From a very young age I liked science, but I have always had a split heart between physics and mathematics and literature and history. Since I was little, I also liked teaching, and my classmates know that in exchange for a snack I gave classes to whoever asked me. In the end I opted for mathematics and physics, because I was attracted to knowing when and why things happened, and since then I have dedicated much of my time to continue learning about the world around us and reading books in my spare time. literature and history, the mountains and gardening. I have always had the support of my family and friends who have understood and supported a woman dedicating herself to a field that until a few years ago was traditionally masculine and now is no longer. Just to say that among my colleagues we are equal parts men and women. I have a fantastic family and being a mother has made me value even more the things I do and what I dedicate my time to. That is why I know that dedicating myself to research and teaching is something fantastic and that it fills me with gratitude to know how lucky I am.

I started my Engineering career in the specialty of structures and then the doctorate in Biomechanics, the branch of Engineering that applies the principles of Mechanics to Life Sciences such as Biology, Veterinary Medicine and Medicine. I was especially attracted to this field because I find that applying Engineering to something as warm and rewarding as trying to improve people’s lives every day is an exciting profession, developing diagnostic, treatment and/or surgical techniques, medical instruments and devices and treating to contribute a grain of sand to make this world better. In my work I live surrounded by great people, I love meeting new people, helping to train new scientists and enriching myself with knowledge.

I am delighted to participate in this initiative with my colleagues, all of them fantastic scientists who in their day to day show that science is open to women and that it is a fascinating way to make this world a little better.”

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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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Nanoligent, whoes founders are leaders of NANBIOSIS units, raises €1M in Series Seed financing

Barcelona, Spain – Milan, Italy, February 3rd, 2022 – Nanoligent SL, a biotech company specialized in the development of nanotechnology-based cancer treatments, today announces the completion of the first closing of a Seed financing round of €1M. The round has been led by members of Italian Angels for Growth, the largest network of business angels in Italy, through the investment vehicle Nanolinvest, and AVANTECA Partners, a Swiss privately held asset management firm, both specialized in supporting innovative early-stage life-science companies primarily in Europe. An equity campaign, is still ongoing on Doorway, an online investment platform, thus promising to provide additional funding for the company.

NANOLIGENTis spin off from the Universidad Autónoma de Barcelona and Research Institute of the Hospital de Sant Pau – IIB Sant Pau that was created by the Directors of NANBIOSIS Units U18. Nanotoxicology Unit, Ramón Mangues and U1. Protein Production Platform (PPP), Antoni Villaverde, together with Esther Vázquez and Manuel Rodriguez

Nanoligent, is focused on the development of new drugs for the treatment of more than 20 different metastatic cancer types. The lead molecule is based on the targeted elimination of cancer cells overexpressing the CXCR4 receptor, a recognized biomarker for poor prognosis and therapy resistance. Nanoligent is developing a new proprietary nano-technological platform, with the potential to overcome current limitations of Antibody-Drug-Conjugates. The CXCR4 is overexpressed in a significant number of patients of more than 20 different tumors.

The financing will allow Nanoligent to complete the pre-clinical development in a variety of tumor types and to move its lead candidate into pre-IND stage.

The investor syndicate will join the Nanoligent’s Board which will consist of: Michele Marzola (IAG), Michael Milos (Avanteca Partners), Manuel Rodríguez (Chairman) and Montserrat Cano (CEO).

“We started the evaluation of a possible investment in Nanoligent one year ago and since then we have received enthusiastic responses from Key Opinion Leaders and Industry Experts. It has been a real pleasure working with the team at Nanoligent; we are impressed by their scientific depth and professional responses. We are continuing our fundraise for this deal together with Doorway, a fintech investing platform”, said Michele Marzola who together with Alessandro Toniolo are co-champions from IAG in this investment.

“We are fascinated by the technological capabilities of the platform and the professionalism of the team. The whole process was an intense, productive and very professional exchange. We are looking forward to partner with the management of Nanoligent to develop this highly innovative platform, which has the potential to transform cancer therapy” said Michael Milos from AVANTECA Partners.

“It is our great pleasure to welcome Michele Marzola and Michael Milos, whose expertise and experience will be a valuable addition to the company to accomplish its ambitious development plans over the next 18 months” said Montserrat Cano, CEO of Nanoligent.

Doorway, at its turn, is very happy to continue fundraising with its qualified community for such an innovative technology that can achieve a significant impact in the treatment of many cancers, being Nanoligent a perfect example of Doorway’s vision of “business with an impact”.

About Nanoligent

Nanoligent was founded in 2017 by co-founder and Chairman Manuel Rodriguez Mariscal, as a spin-off coming from more than 10 years of fruitful collaboration between the Nanobiotechnology group at the Institute of Biotechnology and Biomedicine, Universitat Autònoma de Barcelona, co-lead by full professor Antonio Villaverde and Principal Investigator Esther Vázquez, and the Oncogenesis and Antitumor Drug Group at the Biomedical Research Institut Sant Pau of the Hospital de la Santa Creu i Sant Pau, headed by full professor Ramon Mangues, the three of them also co-founders of the company. Montserrat Cano joined the company in 2020, with more than 15 years of experience in pharma and biotech companies. The aim of the company is to develop a pioneering technological platform based on protein-drug nanoconjugates to target metastasis across several tumor types.

 About Italian Angels for Growth

IAG, founded in 2007, is a leader in the Italian seed venture capital: more than 270 protagonists of the entrepreneurial, financial and industrial world that invest time, skills and capital for the growth of innovative startups. Italian Angels for Growth, in more than ten years of activity, has analyzed more than 6,500 startups and its members have made over 100 investments, for a total of over 300 million euros invested by IAG members and co-investors. IAG business angels support innovative projects financially by investing their own capital, but at the same time, thanks to the mix of skills of the members, support the founders of the startups in the definition of the business model in all its aspects.

 About AVANTECA Partners

AVANTECA Partners is a Swiss-based, privately held asset management company that invests in early-stage life science companies.

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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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