News U6

New Consequences in Familial Hypercholesterolemia due to Abnormal LDL

Misfolded ApoB100 in LDL promotes plaque buildup in familial hypercholesterolemia, raising cardiovascular risk. Structural preservation may aid prevention.

Barcelona, febrero 2025. As recently published in the ICMAB webpage, a new study links ApoB100 protein structure (a key protein found in low-density lipoprotein, LDL, often called “bad cholesterol”) to increased cardiovascular risk in familial hypercholesterolemia. The study, led by IIBB-CSIC and CIBER, with the contribution of ICMAB’s SOFT Service (with NANBIOSIS Unit 6 at its core), shows that the protein structure directly contributes to an increased tendency to aggregate and form atherosclerotic plaques in patients with familial hypercholesterolemia.

In these patients, LDL particles are smaller due to their high content of esterified cholesterol, and ApoB100 has a less flexible structure due to its high percentage of rigid alpha-helices. Developing strategies to preserve the structure of ApoB100 could be a new way to reduce the risk of cardiovascular disease in these patients.

ApoB100 protein structure drives LDL accumulation and increases cardiovascular risk, study finds

This new multicenter study reveals why the structure of the ApoB100 protein, present in LDL along with the so-called “bad cholesterol,” plays a crucial role in the tendency of LDL to accumulate in the arterial walls of patients with familial hypercholesterolemia, thus promoting the formation of atherosclerotic plaques.

The study is led by Vicenta Llorente Cortes, a researcher at the Biomedical Research Institute of Barcelona (IIBB-CSIC) and CIBER-CV, and Valerie Samouillan, a researcher at the University of Toulouse Paul Sabatier.

Familial hypercholesterolemia is a fairly common genetic disorder, affecting about 1 in every 200 or 300 people. Those affected have high levels of low-density lipoprotein (LDL) cholesterol from birth and consequently have a higher risk of cardiovascular diseases and greater rates of premature death due to these conditions.

But, why do LDL particles aggregate more in these individuals? Are there biochemical and physical differences that explain this? This is what the study, published a few weeks ago in the Journal of Lipid Research, aimed to clarify. The study involved 10 research centers in Spain and France. These include, in addition to IIBB-CSIC and CIBER, the Institute of Materials Science of Barcelona (ICMAB-CSIC), the Sant Pau Research Institute (IR Sant Pau), the Autonomous University of Barcelona (UAB), the CIRIMAT Institute (Toulouse, France), and the Miquel Servet Hospital in Zaragoza.

ApoB100 Structure: Less flexible in small, dense LDL particles in patients with familial hypercholesterolemia

LDL particles in patients with familial hypercholesterolemia show a greater tendency to aggregate and form plaques. This is due, explains Vicenta Llorente Cortes, “to the fact that the ApoB100 protein in LDL has a particular structural conformation, with a high percentage of rigid alpha-helices [secondary structures], compared to LDL from healthy patients.”

Using samples from 35 patients with familial hypercholesterolemia and 29 healthy individuals as a control group, the researchers demonstrated that in patients with familial hypercholesterolemia, the protein present in LDL is smaller due to its high content of esterified cholesterol and has less structural flexibility compared to LDL from healthy individuals. As a result, these LDL particles have a lower ability to recover their structure at the arterial intima, promoting their accumulation on the inner walls of the arteries.

Various Techniques to Study LDL Particles

The study measured, among other things, the ease with which LDL particles aggregate using dynamic light scattering techniques (measured at the SOFT Service at ICMAB-CSIC, Unit 6 of NANBIOSIS), as well as the size, composition, and structure of LDL particles through electron microscopy.

As Llorente explains, one of the most impactful findings was the discovery of the difference in the percentage of flexible secondary structures in ApoB100 from patients with familial hypercholesterolemia, which would not have been possible without the collaboration of the biophysics group led by Valerie Samouillan (University of Toulouse). This group applied the FTIR infrared spectroscopy technique to determine the protein’s structure and, in particular, quantify the stable alpha-helices and flexible alpha-helices in LDL from control and patient groups.

The results suggest that developing strategies to structurally preserve ApoB100, and in particular the percentage of flexible alpha-helices in LDL, could be a new way to reduce the risk of cardiovascular disease in patients.

This finding offers a new perspective on how alterations in ApoB100 structure can directly influence the risk of developing cardiovascular diseases. Furthermore, it opens possibilities for designing specific therapies aimed at modulating the content of flexible alpha-helices in LDL, contributing to the prevention of atherosclerosis.

“With these new peptide tools, we aim to preserve the structural flexibility of the ApoB100 protein in LDL from patients with familial hypercholesterolemia.”
Vicenta Llorente

“In our research group,” adds Vicenta Llorente, “we are comparing whether PCSK9 inhibitors [a type of drug] can help preserve the percentage of flexible alpha-helices and whether these effects are comparable to those achieved through innovative peptide tools developed in our group specifically for this purpose. With these new peptide tools, we aim to preserve the structural flexibility of the ApoB100 protein in LDL from patients with familial hypercholesterolemia.”

ICMAB and NANBIOSIS contribution

Amable Bernabé, technician at the SOFT Service of ICMAB-CSIC, and part of NANBIOSIS (Unit 6), played a key role in this study, contributing to the analysis of LDL particle size using the dynamic light scattering (DLS) (Zetasizer) technique. He also participated in the development of the analysis method, interpreting the results, discussing them, and proposing complementary techniques to make the study more robust.

The SOFT Service offers state-of-the-art equipment and technical support for the preparation and characterization of micro- and nanostructured soft molecular materials. This includes molecular surfaces, micro- and nanoparticulate materials, plastic films, dispersed systems, and self-assembled monolayers (SAMs). These materials have applications across various fields, including biomedicine, electronics, energy storage, and other chemical and materials sciences.

Reference article:

Maria Teresa La Chica Lhoëst, Andrea Martínez, Eduardo Garcia, Jany Dandurand, Anna Polishchuk, Aleyda Benitez-Amaro, Ana Cenarro, Fernando Civeira, Amable Bernabé, David Vilades, Joan Carles Escolà-Gil, Valerie Samouillan, Vicenta Llorente-Cortes.
ApoB100 remodeling and stiffened cholesteryl ester core raise LDL aggregation in familial hypercholesterolemia patients.
Journal of Lipid Research. 2025 Jan;66(1):100703. DOI: 10.1016/j.jlr.2024.100703

Watch the following video for more information:

More information about the publication can be found here. This article is a reproduction with a slight edition that does not alter the overall message.

What is NANBIOSIS?

The goal of NANBIOSIS is to provide comprehensive and integrated advanced solutions for companies and research institutions in biomedical applications. All of this is done through a single-entry point, involving the design and production of biomaterials, nanomaterials, and their nanoconjugates. This includes their characterization from physical-chemical, functional, toxicological, and biological perspectives (preclinical validation).

In order to access our Cutting-Edge Biomedical Solutions with priority access, enter our Competitive Call here.

NANBIOSIS has worked with pharmaceutical companies of all sizes in the areas of drug delivery, biomaterials and regenerative medicine. Here are a few of them:

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A Breakthrough Therapy for Fabry Disease: nanoGLA Demonstrates Promising Results

Fabry disease therapy nanoGLA, developed by NANBIOSIS and our partners, shows superior efficacy in preclinical trials, targeting systemic and brain symptoms.

Barcelona, january 2025. An international research team led by the Institute of Materials Science of Barcelona (ICMAB-CSIC) and CIBER-BBN, in collaboration with the Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), has developed a groundbreaking nanotechnology-based therapy called nanoGLA for the treatment of Fabry disease. The innovative solution has shown remarkable efficacy in preclinical studies and has been published in the open-access journal Science Advances (see below for reference links).

What is Fabry disease?

Fabry disease is a rare genetic disorder caused by a deficiency of the enzyme α-galactosidase A (GLA). This deficiency leads to the accumulation of fatty substrates (mainly globotriaosylceramide or Gb3) in cells, resulting in severe damage to various organs. The nanoGLA therapy employs peptide-guided nanoliposomes to deliver the deficient GLA enzyme effectively to the organs most affected by the disease. Researchers have successfully produced nanoGLA at the quality and scale required for preclinical trials, paving the way for clinical testing.

GLA inside nanoliposomes: nanoGLA

In studies with mouse models of Fabry disease, nanoGLA demonstrated superior efficacy compared to therapies using the non-encapsulated enzyme. It effectively targeted affected organs and, notably, the brain — a critical achievement that current therapies cannot match. These findings underscore nanoGLA’s potential to address both systemic and cerebrovascular manifestations of Fabry disease.

Highlighting the importance of this innovation, the European Medicines Agency (EMA) granted nanoGLA the Orphan Medicinal Product Designation in 2021, a significant milestone in its development.

The contribution of NANBIOSIS to this project was regarding the synthesis, processing and nanostructuring of the formulation (Unit 3 and Unit 6), and the preclinical assays using Fabry disease mouse models (Unit 20). Remember that if you want to collaborate with us, we are at the final stretch of our Open Call!

The product of scientific collaboration

This breakthrough is the result of collaborative efforts in which NANBIOSIS played a crucial role. These involve multiple international institutions, including ICMAB-CSIC, CIBER-BBN, Vall d’Hebron Research Institute (VHIR), and companies such as Nanomol Technologies SL and Leanbio SL, as well as IQAC-CSIC, the Institute of Biotechnology and Biomedicine (IBB-UAB), and international partners like Joanneum Research–Institute for Biomedical Research and Technologies (HEALTH) (Austria), Technion-Israel Institute of Technology (Israel), Guangdong-Technion Israel Institute of Technology (China), Aarhus University (Denmark), and Labcorp Drug Development (UK).

“The nanoGLA formulation represents a promising opportunity for Fabry disease patients, especially in addressing neurological symptoms, which current therapies fail to tackle.”
Elisabet González, ICMAB researcher and lead author

“The nanoGLA formulation represents a promising opportunity for Fabry disease patients, especially in addressing neurological symptoms, which current therapies fail to tackle,” said Elisabet González, researcher at ICMAB and one of the study’s lead authors. “Our goal is to develop safer and more effective treatments by harnessing the potential of nanotechnology.”

The bright future of this research

The research was conducted within the framework of the European project Smart4Fabry, funded by the European Union’s Horizon 2020 research and innovation program. Building on these promising results, the European Commission has provided further funding through the EU Phoenix and Nano4Rare projects to complete the preclinical phase and secure approval to begin clinical trials with human patients.

For more information, refer to the original study: “Targeted nanoliposomes to improve enzyme replacement therapy of Fabry disease,” published in Science Advances, Vol. 10, Issue 50, DOI: 10.1126/sciadv.adq4738.

This article was adapted from the press release by ICMAB. Press contact: communication@icmab.es. Institut de Ciència de Materials de Barcelona (ICMAB, CSIC).

What is NANBIOSIS?

In order to access our Cutting-Edge Biomedical Solutions with priority access, enter our Competitive Call here.

NANBIOSIS has worked with pharmaceutical companies of all sizes in the areas of drug delivery, biomaterials and regenerative medicine. Here are a few of them:

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The Soft Lab held a new edition of the course on characterization and preparation of particulate materials

José Amable Bernabé, Technical Coordinator of Unit 6, hosted a course on “Characterization techniques for particulate materials”.

Barcelona, october 2024. For yet another year, José Amable Bernabé, of the Soft Materials Service at ICMAB and Technical Coordinator of NANBIOSIS Unit 6, offered this course. The course was an explanation of different techniques to characterize nanoparticles and particulate matter, including the fundamentals of these techniques, sample preparation, practical examples and results interpretation.

The course is offered every year through the CSIC training courses offered every year for all its staff, as reported in ICMAB webpage.

Soft Materials Service

The Soft Materials Service 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.

On April 2022, the Service Materials Service, which is part of our Unit 6, 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.

Amable Bernabé showing the materials' characterization equipment to the course participants — Amable Bernabé showing the materials’ characterization equipment to the course participants. Source: ICMAB webpage.

What is NANBIOSIS?

In order to access our Cutting-Edge Biomedical Solutions with priority access, enter our Competitive Call here.

NANBIOSIS has worked with pharmaceutical companies of all sizes in the areas of drug delivery, biomaterials and regenerative medicine. Here are a few of them:

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Reaching for the unreachable: New efforts to treat Lysosomal Storage Diseases

NANBIOSIS researchers pioneer novel treatments for Lysosomal Storage Diseases utilizing extracellular vesicles and liposomes, offering hope to patients.

1 March 2024, Vall d’Hebron Research Institute/ICMAB-CSIC (Barcelona)

Lysosomal Storage Diseases (LSDs) encompass a group of rare disorders caused by mutations in lysosomal proteins. These mutations can lead to dysfunctional proteins responsible for breaking down cellular materials, resulting in the accumulation of deposits. Such accumulations can manifest in various neurological symptoms, ranging from progressive neurodegeneration to severe cognitive impairment. Often emerging in childhood, LSDs tragically culminate in premature death for many patients.

Currently, up to 14 subtypes of LSDs can be treated using Enzyme Replacement Therapy (ERT). This therapy involves repeated intravenous administrations of non-mutated proteins to replace the dysfunctional protein that the patient naturally produces. However, this treatment modality is effective only for diseases caused by enzyme mutations. Moreover, intravenously administered enzymes often fail to reach the brain, leaving patients with neurological manifestations of LSDs untreated.

In response to this, the Clinical Biochemistry, Drug Delivery & Therapy (CB-DDT) group at VHIR (in which the Unit 20 of NANBIOSIS is integrated) is playing a pivotal role in acknowledging this issue. Our researchers are pioneering the use of Extracellular Vesicles (EVs) to deliver functional lysosomal proteins to affected cells and organs. EVs, which are tiny particles naturally utilized by cells for intercellular communication, offer a promising avenue as drug delivery systems. The project, which will culminate this year 2024, aims to engineer EVs for enhanced protein delivery and selectivity. This potentially addresses LSDs with a neurological manifestation, and allows to more effectively reach key affected organs, like in the case of heart and kidneys in Fabry disease [1]. Moreover, this technique could also set the stage for treatments aiming to address LSDs caused by transporter deficiencies, another remaining challenge of these dreaded genetic conditions.

The results of this fruitful collaboration between Units 6 and 20 have derived in the generation of our “Enzyme-loaded Nanovesicles” service, one of the flagship Cutting-Edge Biomedical Solutions of NANBIOSIS.

The role of liposomes:

Additionally, the CB-DDT group is collaborating with the NANOMOL group at ICMAB, home of NANBIOSIS Unit 6. Thanks to this collaboration, the researchers managed to explore the use of liposomes, a type of synthetic nanoparticle, as a targeted therapeutic vehicle to enhance ERT effectiveness.

The results of this fruitful collaboration between Units 6 and 20 have derived in the generation of our “Enzyme-loaded Nanovesicles” service, one of the flagship Cutting-Edge Biomedical Solutions of NANBIOSIS. This allows our clients to precisely load enzymes into nanovesicles, which can be applied in targeted therapies for various disorders. This service includes direct applications in many rare diseases, but it can be expanded to any application that requires a well-defined nanovesicle. You can check more information about this Cutting-Edge Biomedical Solution here.

The ongoing research and multiple collaborations hold promise not only for improving current therapies but also for expanding treatment options for LSD patients. This could potentially offer hope where there was previously none. As the collaboration between VHIR and ICMAB continues to yield groundbreaking insights, the future of LSD treatment appears increasingly optimistic.

This article is in the context of Rare Disease Day 2024. To stay up to date, visit our news section here.

References:

[1] Seras-Franzoso J, Díaz-Riascos ZV, Corchero JL, González P, García-Aranda N, Mandaña M, Riera R, Boullosa A, Mancilla S, Grayston A, Moltó-Abad M, Garcia-Fruitós E, Mendoza R, Pintos-Morell G, Albertazzi L, Rosell A, Casas J, Villaverde A, Schwartz S Jr, Abasolo I. Extracellular vesicles from recombinant cell factories improve the activity and efficacy of enzymes defective in lysosomal storage disorders. J Extracell Vesicles. 2021 Mar;10(5):e12058. doi: 10.1002/jev2.12058. Epub 2021 Mar 12. PMID: 33738082; PMCID: PMC7953474.

Additional information:

In order to access our Cutting-Edge Biomedical Solutions, place your request here.

NANBIOSIS has worked with pharmaceutical companies of all sizes in the areas of drug delivery, biomaterials and regenerative medicine. Here are a few of them:

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The NABIHEAL Project Pioneers Wound Healing with New Biomimetic Matrices

Nearly 40 scientists across 7 countries are pioneering this breakthrough in wound healing using a nobel and affordable bio-inspired, anti-bacterial matrix.

In addition to the vast consortium, the project also comprises 5 small and medium-sized enterprises (SMEs) and 9 academic institutions. These were convened last February at the University of Granada to share insights, progress, and strategies.

According to an article published by UGR at the beginning of this month, about 40 researchers involved in the project have attended a meeting to share results and progress.

The Horizon Europe project NABIHEAL, coordinated by the Biomedical Research Networking Center (CIBER) at the Institute of Materials Science in Barcelona (ICMAB, CSIC), has held a consortium meeting. The international consortium consists of 14 partners from 7 countries, including 5 small and medium-sized enterprises (SMEs) and 9 academic institutions. These partners have expertise in the development, evaluation, and commercialization of products for wound healing, nanotechnology, safety, and regulation.

Who are the NABIHEAL project partners?

There are three groups from CIBER-BBN participating within NABIHEAL: two groups correspond to Unit 6 and Unit 16 of NANBIOSIS. The former is the NANOMOL Group, and is lead by Nora Ventosa, the project coordinator of NABIHEAL. The later corresponds to our Surface Characterization Unit from UEx. The third CIBER-BBN group is the Photonics Engineering Group (GIF) from the University of Cantabria, with several of its leaders working at NABIHEAL.

In addition, researchers from the UGR’s Advanced Therapies: Differentiation, Regeneration, and Cancer group, as well as the Clinical and Translational Dermatology group, are participating as one of the partners in this consortium. Both belong to the ibs.GRANADA Biosanitary Research Institute and the UGR’s Modeling Nature: from nano to macro Excellence Unit.

Professor Juan Antonio Marchal Corrales leads the project at the UGR and is part of the project’s steering and executive committees. This project is developed at the Singular Laboratory of Biofabrication and 3D (bio)printing (BioFabi3D), located at the Biomedical Research Center (CIBM). In addition, UGR and ibs.GRANADA, in collaboration with the company Bioibérica, contribute their expertise in the biofabrication and 3D bio-printing of human skin models based on components of the matrix of each of the skin layers.

About the meeting at UGR:

The meeting, held on February 7th and 8th, was inaugurated by the project coordinator, Nora Ventosa, Scientific Director of Unit 6 of NANBIOSIS and researcher at a researcher at CIBER and ICMAB-CSIC, and by Enrique Herrera, the Vice-Rector for Research and Technology Transfer of the University of Granada.

The meeting was attended by 38 researchers from among the NABIHEAL partners. These included the Biomedical Research Networking Center (CIBER) at the Institute of Materials Science in Barcelona (ICMAB); the University of Extremadura and the University of Cantabria; the Spanish National Research Council (CSIC); Nanomol Technologies S.L. (NT); Bioiberica S.A.U (BIO); Histocell S.L (HCELL); Asphalion (ASPH); MyBiotech GmbH (MyB); Charité-Universitätsmedizin Berlin (CH) from Germany; the Institute for Medical Research and Occupational Health (IMI) from Croatia; the University of Aarhus (AU) from Denmark; the Technion-Israel Institute of Technology (IT) from Israel; BioNanoNet Forschungsgesellschaft mbH (BNN) from Austria, and the University of Maribor (UM) from Slovenia, as reported by the UGR.

About NABIHEAL project:

NABIHEAL, “Nanostructured Antimicrobial Biomaterials for Healing Complex Wounds,” is funded by the Horizon Europe Research and Innovation program. It has a total budget of nearly 5 million EUR for the next four years. The project addresses two unmet medical needs in the healing of complex wounds: firstly, affordable treatments for wound infections and prevention of complications during healing, and secondly, a strategy to optimize the composition and efficacy of drugs and dressings for wound healing.

Aim of the project:

Complex wounds affect the quality of life of more than 2% of the population in developed countries. Thus, it is a global health problem with a significant impact on healthcare economics. Moreover, complex wounds, including chronic wounds or major burns, are highly susceptible to microbial infection and biofilm formation, making them difficult to treat. In this regard, silver is a widely used metal in antimicrobial products for treating wound infections. However, silver-based products are expensive and have various drawbacks due to costs and environmental and safety concerns.

The NABIHEAL project will develop multifunctional biomaterials to address some of the unmet medical needs in wound management. This project will provide affordable treatments for wound infections or prevention of complications during all phases of wound healing.

In the short and medium term, NABIHEAL will develop —at least— two innovative multifunctional biomaterials for wound healing, using affordable manufacturing technologies based in the EU. In the long term, NABIHEAL could become an alternative to silver in wound dressing for wound healing.

You can read more about NABIHEAL project at the official webpage here.

Additional information

The goal of NANBIOSIS is to provide comprehensive and integrated advanced solutions for companies and research institutions in biomedical applications. All of this is done through a single-entry point, involving the design and production of biomaterials, nanomaterials, and their nanoconjugates. This goes along with their characterization from physical-chemical, functional, toxicological, and biological perspectives (preclinical validation).

In order to access our biomedical Solutions, apply here.

NANBIOSIS has worked with pharmaceutical companies of all sizes in the areas of drug delivery, biomaterials and regenerative medicine. Here are a few of them:

• Read More

Technical seminar on materials characterisation equipment

The Service-SOFT/U6 Nanbiosis ICTS (of CIBER-BBN and ICMAB-CSIC) together with the company NANE are organising a technical seminar on materials characterisation equipment. In this seminar, different techniques for the characterisation of particulate materials such as DLS, NTA, Laser Diffraction, Morphology will be discussed.

Limited places. You can register at this link

Link to the program: here

Date: 08th of November

Place: Institute of Materials Science of Barcelona (ICMAB) -CSIC – Conference room

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NABIHEAL project launches website

The website for NABIHEAL, an EU-funded Horizon Europe project developing biomaterials for complex wound healing, is now online.

The Horizon Europe project NABIHEALi project is coordinated by the Center for Biomedical Research Network (CIBER) at the Institute of Materials Science of Barcelona (ICMAB-CSIC).

This project will apply one the “Cutting Edge Biomedical Solutions” of NANBIOSIS for the preparation of different nanoestructures with antimicrobial properties, required for the development of the final multifunctional wound healing biomaterials. This case will gather the expertise of two NANBIOSIS unit: NANBIOSIS U6 will produce and characterize these nanoestructures with antimicrobial properties, which will be tested in NANBIOSIS U16.

Find out more about the project and what its impact will be, and browse the 14 partners from 7 countries to see how each contributes to the project’s objectives. NABIHEAL WEBSITE

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A discovery in one of the most aggressive cancers will allow more efficient diagnosis

The extracellular vesicles secreted by triple-negative breast cancer stem cells are markers of lung metastasis, according to a study carried out by researchers at CIBER.

The work has been carried out by researchers from various CIBER-BBN groups (Bioengineering, Biomaterials and Nanomedicia), and CIBERONC (CIBER area focused on cancer) has participated in it. The research has been led by Joaquín Seras, from the Vall d’Hebron Research Institute (VHIR), a specialist in targeted drug therapies.

Physicochemical EVs characterization and all the in vivo studies were performed by NANBIOSISunits of CIBER, specifically NTA analysis was carried out at Unit 6 of Biomaterial Processing and Nanostructuring, led by Nora Ventosa at ICMB-CSIC and animal experimentation at Unit 20 “In vivo experimental platform”, led by Ibane Abasolo at VHIR.

The vesicle, in cell biology, is an organelle that forms a small, closed compartment, separated from the cytoplasm by a lipid bilayer just like the cell membrane. The vesicles store, transport or digest cellular products and waste. According to Joaquin Seras, leader of the research: “the identification of this subpopulation of cancerous extracellular vesicles, and their important role in the progression of the disease, will allow in the future to develop systems more effective and less invasive diagnostic methods based on their detection directly from blood samples”.

In different types of tumors, including triple negative breast cancer, it has been observed that the extracellular vesicles generated by tumor cells play an important role in the generation of pre-metastatic niches. Triple negative breast cancer, one of the most aggressive, highly plastic and heterogeneous, is characterized by a significant presence of malignant stem cells.

The study carried out by the Spanish researchers from CIBER with promising results, published in the “International Journal of Cancer”, shows, both in in vitro and in vivo models of the disease, that the vesicles actively contribute to the formation of areas with favorable conditions for the formation of metastases, thus favoring way, the spread of the disease.

Research contributions
In the opinion of Joaquin Seras, the great contribution of this work is that it “describes how the extracellular vesicles secreted by certain subpopulations of cancer cells, specifically those derived from cancer stem cells, have the potential to modify the microenvironment of the future metastatic niche to promote tumor growth.

In other words, continues the leader of the study: “the research sheds new information on the pathogenic mechanism of the disease, and suggests these extracellular vesicles as markers with diagnostic potential. It should be noted that these nanoparticles are secreted into the bloodstream by tumor cells, and effective capture and identification would allow them to be exploited as a diagnostic tool”.

On the characterization of extracellular vesicles of cancer cells
The complex composition and functional differentiation of cancer cells in a tumor also increases the heterogeneity of the subsets of vesicles secreted by cancer.

This phenomenon is particularly relevant in triple negative breast cancer, one of the most aggressive, highly plastic and heterogeneous cancers, characterized by a significant presence of malignant stem cells. However, until now the diversity of the vesicles secreted by cancer cells had not been studied, a diversity that is closely related, in turn and as the study shows, to cellular heterogeneity in triple-negative tumors.

The importance of the CIBER study lies at this point: the vesicles secreted by different tumor subpopulations and grouped by their degree of differentiation show fundamentally different activities in terms of their impact on cancer progression.

In the investigation, the extracellular vesicles secreted by up to three different types of neoplastic cells have been isolated and characterized, observing different bioburdens for each type, with the consequent differential effect on stromal cells. In addition, and as the study shows, cancer stem cell-derived vesicles contribute to converting healthy lung cells into receptive niches for the metastatic growth of cancerous breast cells.

Article reference:

González-Callejo P, Gener P, Díaz-Riascos ZV, Conti S, Cámara-Sánchez P, Riera R, Mancilla S, García-Gabilondo M, Peg V, Arango D, Rosell A, Labernadie A, Trepat X, Albertazzi L, Schwartz S Jr, Seras-Franzoso J, Abasolo I. Extracellular vesicles secreted by triple-negative breast cancer stem cells trigger premetastatic niche remodeling and metastatic growth in the lungs. Int J Cancer. 2023 Jan 27. doi: 10.1002/ijc.34447. Epub ahead of print. PMID: 36705298.

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Nanoparticles to modulate topography and ligand distribution at the nanoscale: impact on cell behavior

Doctor Marc Martínez from the Nanomol-Bio group – NANBIOSIS U6 from CIBER-BBN at ICMAB-CSIC, defended his PhD thesis “Nanoparticles to modulate topography and ligand distribution at the nanoscale: impact on cell behavior” on 9 March 2023 at ICMAB.

he PhD thesis was supervised by Imma Ratera, Judith Guasch and Nora Ventosa from the Nanomol-Bio group at ICMAB-CSIC.

Ana Paula Candiota Silveira, Scientific Coordinator of NANBIOSIS U25 was part of the Committee that evaluated the Thesis tooghether with Jesús Martínez de la Fuente, Instituto de Nanociencia y Materiales de Aragón (INMA-CSIC) (President), and Anna Lagunas Targarona, Institut de Bioenginyeria de Catalunya (IBEC) (Vocal).

As Marc Martínez explained in an inteview to ICMAB “I produce nanoparticles in the lab and I use them to see how cells react to them. I work at the interface between cells and materials. My research can be applied to cell culture, which can be relevant for the development of new therapies for the regeneration of organs or for building implants to replace missing organs and body parts”.

Doctor Marc Martínez’s PhD thesis was part of the PhD Programme in Biochemistry, Molecular Biology and Biomedicine from the Universitat Autònoma de Barcelona (UAB).

Further information at ICMAB webpage

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Advancing a novel nano-pharmaceutical towards clinical translation

Prof Nora Ventosa, Scientific Director of NANBIOSIS U6 “Biomaterial Processing and Nanostructuring Unit” from CIBER-BBN and ICMAB-CSIC) is hosting the Lecture on nano-pharmaceuticals: “Advancing a novel nano-pharmaceutical towards clinical translation” by Elisabet González, from Nanomol-Bio Group of ICMAB-CSIC and CIBER-BBN

Monday, 13 February 2023
12 PM – 15 PM
ICMAB – Sala d’Actes Carles Miravitlles and ONLINE

Registration and futher information

Abstract: Nano-pharmaceuticals have the potential to drive the scientific and technological uplift, offering great clinical and socio-economic benefits to the society in general, industry and key stakeholders and patients. However, the translation of nano-pharmaceuticals from lab bench to an advanced stage of pharmaceutical development faces significant challenges: the high quality and quantity of these novel nanoformulations required for the preclinical (and further clinical) testing, the tight standards and regulations that must be complied with in this pharmaceutical field, and the increasing costs as development progresses, entails the major challenges, especially considering that the main players are usually research groups, spin-offs from academia or SMEs.

In this context, publicly funded research investment led by the European Commission within the framework of the Horizon Europe Programme is contributing to foster the transition from basic science to clinical practice. For example, by means of the EUH2020 Smart-4-Fabry Project (2017-2020), a novel nanomedicine for the Fabry disease treatment was developed up to an advance stage of preclinical development. For that, crucial considerations for early-stage product development were taken into account: these included identifying those critical quality attributes of the drug product essential for activity and safety, development and validation of advanced analytical methods (physical, chemical, biological) for characterization and quality control, identification and control of process parameters to ensure consistent batch-to-batch reproducibility, up-scaling manufacturing, and the use of adequate preclinical models.

Additionally, close collaboration with regulatory agencies from the early stages of development was carried to assure an aligned position and obtain a solid proof-of-concept. The outstanding efficacy results in preclinical models permitted to obtain an important milestone with strong implications for the translation of this new therapeutic product from bench to bedside: the Orphan Drug Designation by the European Medicines Agency (EMA). Currently, with the EU H2020 Phoenix Project (2021-2025), which aims to establish a Pharmaceutical Open Innovation Test Bed, together with the Project Innova4Fabry (2022-2023) from Innovators program (AGAUR), which aims to create a spin-off company, a smooth transfer of this novel therapy to clinical phase is pursued.

Dr. Elisabet González is senior researcher at the Nanomol-Bio group from ICMAB-CSIC and CIBER-BBN. She has extensive training in the field of Pharmaceutical Sciences. After the graduation of BSc in Pharmacy (2003), she held the MSc in Drug Research, Development and Control (2007), and the PhD in Pharmacy from the University of Barcelona (UB) (2011). Her 15+ years of scientific activity have been focused on the design of new type of nanoparticulate systems for technologically advanced applications in biomedicine (ocular and dermal inflammatory diseases, complex wounds, rare congenital metabolic diseases…).

Her pharmaceutical expertise has contributed to manage and coordinate multidisciplinary activities in the frame of national and international projects, which cover all key stages of the pharmaceutical development: from the design, manufacturing, characterization and quality control of nanoformulations to the preclinical and clinical development, and regulatory considerations. To highlight, she has played a key role in advancing the development of two effective nanoformulations from an experimental proof of concept (TRL3) to an advanced stage of preclinical development (TRL5), enabling with her first hand scientific-technical coordination the entrance of these nanoformulations to the regulatory preclinical phase.

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