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News U20

News U20

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:

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, 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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New upcoming events: The active role of NANBIOSIS in awareness of rare diseases

For Rare Disease Day, we raise awareness through 2 events: 1 in Barcelona (Feb 28) & another in Madrid (Feb 29). Collaboration & research in focus.

28-29 February 2024, Rare Disease Day 2024

NANBIOSIS is actively involved in promoting awareness and understanding of rare diseases, Due to their lower incidence, these conditions are often face neglect in medical research and industrial treatment. To spotlight this crucial issue, NANBIOSIS is pleased to announce its participation in two significant events coinciding with Rare Disease Day celebrations. These events will address various aspects of rare and minority diseases research and treatment.

Event 1: February 28th at Vall d’Hebron, Barcelona

On February 28th, NANBIOSIS will contribute to the Rare Diseases Symposium at Vall d’Hebron Hospital in Barcelona. This event, available for both in-person attendance and online viewing, will commence at 10:00 and feature a series of informative talks until 12:25.

Held at the Auditorium (10th floor) of Vall d’Hebron General Hospital (Pg. de la Vall d’Hebron, 119, Horta-Guinardó, 08035 Barcelona, Spain), the symposium will explore rare diseases across different life stages, with a focus on the role of new technologies in diagnosis and the importance of informed consent.

Members from the group of Clinical Biochemistry, Drug Delivery & Therapy (CB-DDT), in which NANBIOSIS Unit 20 is integrated, are proud to be a part of this event.

To read the full programme of the event, click here. To find more information about the event and to follow it online, follow this link.

Researchers from Clinical Biochemistry, Drug Delivery & Therapy (CB-DDT) at Vall d’Hebron, in which NANBIOSIS Unit 20 is integrated.

Event 2: February 29th at CaixaForum, Madrid

The XIII edition of the CIBERER Day “Research is Progressing” will take place on February 29th from 15:30 to 19:30 at the Auditorium of CaixaForum Madrid (Paseo del Prado 36).

Led by Pablo Lapunzina, Scientific Director of CIBERER, this event will showcase the latest advancements from the center. CIBERER, a part of CIBER, which houses CIBER-BBN, one of the three institutions comprising NANBIOSIS. The event will also feature presentations on collaborative initiatives between CIBERER researchers and patient associations, followed by a panel discussion on the role of biobanks in rare disease research.

For more information about his event, including attendance, click here.

These events reflect NANBIOSIS’s ongoing commitment to advancing research and treatment options for rare diseases, highlighting the importance of collaboration in addressing these often overlooked conditions.

To stay up to date, visit our news section 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 includes 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:

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Polymeric Micelles Delivering Hope: A Revolutionary Strategy to Fight Cancer

NANBIOSIS researchers reach intracellular targets with encapsulated antibodies.

February 2024, IQAC-CSIC/CIBER-BBN, Barcelona (Spain) and Santiago (Chile)

Dr. Abasolo and her team have developed an innovative strategy to combat intracellular oncogenes, notably KRAS, implicated in various deadly cancers. By encapsulating therapeutic antibodies within polymeric micelles, they have successfully facilitated the entry of these antibodies into cancer cells, targeting internal markers. This breakthrough, achieved through international collaboration, represents a significant advancement in cancer treatment and holds promise for addressing other diseases with intracellular targets. These findings provide hope for improved therapies and outcomes in cancer and beyond.

Every individual is said to have an inner enemy, lurking to sabotage under favorable circumstances. In the case of our cells, this rings particularly true. Some genes are as necessary for their proper function as they are dangerous when they malfunction. Those that, under certain circumstances, promote tumor development are known as oncogenes. But we now have new tools to combat them.

In the ongoing battle against cancer, researchers have reached a significant milestone in combatting intracellular oncogenes. Thanks to a groundbreaking strategy developed by Dr. Abasolo and her team from Unit 20, they managed to reach particularly difficuly intracellular targets. Their innovative approach involves utilizing therapeutic antibodies encapsulated in polymeric micelles, facilitating their entry into cancer cells and targeting internal markers. The results, achieved through international collaboration, mark a significant advancement in cancer treatment and hold promising possibilities for addressing other diseases with intracellular targets.

KRAS is the name given to one of these oncogenes, and it’s a particularly dangerous foe. The small protein produced by the KRAS gene is a molecular switch that controls numerous cellular functions, including survival, proliferation, differentiation, and migration. When KRAS mutates, this switch stops working, preventing the cell from self-regulating, often leading to some of the most malignant and lethal types of cancer, such as pancreatic, colon, or lung cancer. Moreover, this mutated protein is difficult to target due to its unique molecular structure and the fact that it resides within the cell. However, thanks to our new anti-tumor technology, we’re able to reach it.

One method of blocking mutated KRAS is through the use of therapeutic antibodies. These antibodies, by specifically binding to the protein, inhibit its function, halting the malignancy of cancer cells. However, one of the challenges in using these antibodies is that they cannot enter cells on their own. None of the attempts to internalize them have been successful, until now.

In a recent study published last year, the team led by Dr. Abasolo, in which our Unit 20 is integrated, has successfully attacked mutated KRAS using anti-KRAS antibodies. To achieve this, they encapsulated the antibodies in nanometric drug delivery systems (NanoDDS). Specifically, they used micelles composed of a polymer capable of surrounding the antibodies, facilitating their entry into cells. Furthermore, these nanostructures enable passive and selective entry into tumors and, to top it off, the polymer used prevents the emergence of dreaded cancer multi-drug resistances.

These unprecedented results are the product of international collaboration, where in silico simulation, in vitro assays, and animal studies have gone hand in hand. These results have demonstrated the effectiveness of a new tool capable not only of serving in the fight against cancer, but also of acting on therapeutic intracellular targets present in many other diseases. A way to defeat that inner enemy.

References

[1] Diana Rafael, Sara Montero, Pilar Carcavilla, Fernanda Andrade, Júlia German-Cortés, Zamira V. Diaz-Riascos, Joaquin Seras-Franzoso, Monserrat Llaguno, Begoña Fernández, Alfredo Pereira, Esteban F. Duran-Lara, Simó Schwartz Jr., and Ibane Abasolo. Intracellular Delivery of Anti-Kirsten Rat Sarcoma Antibodies Mediated by Polymeric Micelles Exerts Strong In Vitro and In Vivo Anti-Tumorigenic Activity in Kirsten Rat Sarcoma-Mutated Cancers. ACS Applied Materials & Interfaces 2023 15 (8), 10398-10413 DOI: 10.1021/acsami.2c19897

Additional information

In this project, Unit 20 of the NANBIOSIS ICTS has collaborated, providing both functional validation and all preclinical trials with murine models. All of this has been conducted following the strictest ethical guidelines.

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 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:

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The door is now open to a new nanoparticle-based treatment for chronic liver disease

– It is possible to achieve an administration method that improves the effectiveness and increases the safety of drugs for chronic liver disease?

-Yes, with nanoparticles!

– How?

To find an answer, was created the european project NANOSIM (Biodegradable nanoparticles of Simvastatin as new therapeutic tool for chronic liver disease financed in the Joint Transnational Call (2018) led by the Hospital Vall d´Hebron. A translational research proposed as an approach for its use in patients.

Until now, the only therapeutic option for patients is to eliminate the etiological agent (or the external promoter of damage), whether it is a virus, such as Hepatitis B, or a substance, such as alcohol. Once the agent is eliminated, only preventive treatment of the main associated complications can be carried out, but nothing to prevent or slow down the damage to the liver.

Now, the team behind NANOSIM project has published a study in the journal Pharmaceutics that opens the door to a treatment that specifically targets the sinusoidal endothelial cells of the liver, which are the first inducers of liver damage. The innovation is not a new drug, but a new delivery method that uses nanotechnology so that the drug acts directly on key liver cells.

The study has been led by María Martell, head of the Advanced Chronic Liver Diseases laboratory within the VHIR Liver Diseases group and with the collaboration of Ibane Abasolo, head of the VHIR Clinical Biochemistry, Drug Delivery and Therapy group. The researchers from both groups belong to the Network Biomedical Research Center (CIBER) in the area of Liver and Digestive Diseases (CIBEREHD) and Biomedicine, Biomaterial and Nanomedicine (CIBER-BBN), respectively. The U20 of the ICTS NANBIOSIS has also participated in the study.

Dr. Martell highlights the importance of advancing new and better treatments for cirrhosis: “Chronic liver diseases are the fifth cause of mortality in adults aged 50-70 years and cause 85% of liver transplants. Only in the territory European it is estimated that there are 29 million people affected”.

The research team focused on simvastatin, a drug used as an adjunctive therapy for cholesterol and which had been shown to have a protective function of endothelial cells, which are key to preventing the creation of liver fibrosis that causes liver inflammation. The problem is that oral or intravenous administration of the necessary dose causes a series of side effects, at the muscle and liver level, which limits its use. The goal of the research was to find a way to deliver the drug directly to the endothelial cells of the hepatic sinus without it being able to disperse to other parts of the body and causing unwanted side effects.

This active and specific targeting was achieved by binding polymeric micelles to peptides recognized by the surface marker CD32b, specific for liver endothelial cells. In this way, in in vivo models, a reduction in liver fibrosis was achieved without a significant increase in toxicity and, therefore, an effective and safe method to treat chronic liver diseases.

Dr. Abasolo, Director of NANBIOSIS U20 adds “Once that we have demonstrated the effectiveness of the technology to directly reach the sinus endothelial cells, a wide range of possible medications opens up with which we can use this nanotechnology to improve liver function.”

Article of reference:

Optimization of Statin-Loaded Delivery Nanoparticles for Treating Chronic Liver Diseases by Targeting Liver Sinusoidal Endothelial Cells

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Related news:

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New equipment adquired to improve NANBIOSIS U20

NANBIOSIS, U20. In Vivo Experimental Platform, led by Dr. Ibane Ibasolo, has been updated and improved as a result of its participation in the project FICTS1420-20, selected by the MICINN for co-financing by the FEDER Program in ICTS 2014-2020 (Equipment for setting standardized immunotoxicology assays for the U20 -NANBIOSIS I17 Action of the Investment Plan-)

A particle particle analyzer equipment (Exoid) has been inslalled at NANBIOSIS U20 for measurement of the concentration and the size of nanoparticles. The Exoid is the latest instrument from the Izon company to measure the physical characteristics of nanoparticles in electrolytic solution. Based on Tunable Resistive Pulse Sensing (TRPS) principles, the equipment is capable of measuring the size of the particles, their concentration and Z potential, through the use of a nanopore that allows measurements to be made in a defined size range.

Finally, a new upright laboratory freezer Liebherr _ SFNe 5227 has been adquired for the storage of the samples and reagents used in the different services of FVPR/U20,

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Workshop on Hyperthermic Oncology

Next Friday, June 9, 2023, a Workshop on Oncological Hyperthermia entitled “Clinical Implementation of Oncological Hyperthermia in Spain and Europe: current situation and prospects” will be held in Barcelona. The location of the event is at the Hotel Front Marítim in Barcelona and the scheduled time is from 9:00 a.m. to 5:30 p.m.

Relevant speakers will present an updated vision on the different modalities of hyperthermia that are being used for cancer treatment. Jorge Contreras (Coordinator of the Spanish Society of Radiation Oncology ) will give a session on the current situation of clinical hyperthermia in Spain. Daniel Ortega (Coordinator of the National Network of Nanotechnology in Translational Hyperthermia) and Teresa Macarulla (Coordinating Investigator of the NoCanTher study on the use of magnetic nanoparticles associated with hyperthermia treatment in pancreatic cancer) will present their experience with a nanotechnological health product in said trial. After a break, Giammaria Fiorentini (Director of the Oncology Unit of the Muraglia di Pesaro Hospital) will give a vision of the use of electro-modulated hyperthermia in pancreatic cancer and in a round table, different professionals will give therir global vision of the application of these techniques from preclinical to clinical implementation.

In addition, regulatory aspects will also be covered. Luc van Hove (Medical, Regulatory and Clinical Affairs expert) will speak from a European perspective on the regulation of medical devices and in vitro diagnostics; while Julia Caro (Head of the area of the National Center for Certification of Sanitary Products) will do so from the perspective of a notified body.

Further information and registration at this link: https://forms.office.com/e/0251iMc2LT

There is additional information at:
-Linkedin https://www.linkedin.com/posts/safenmt_hyperthermia-magnetic-barcelona-activity-7062697943509737472-85wP?utm_source=share&utm_medium=member_desktop.
-Twitter https://twitter.com/abasolo_vhir/status/1659074218850484224

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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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Rare diseases international day 2023: some NANBIOSIS contributions

Today is the international day of rare diseases, a day to raise awareness and instigate change for people living with a rare disease. From NANBIOSIS we want to sume to this celebration and higtligh our commitment to helping people with rare diseases through research.

Dr. Ibane Abasolo, Scientific Director of NANBIOSIS U20, was at the WORLDSymposia conference last week in Orlando (FL, USA), where the latest advances in preclinical study and clinic of lysosomal storage diseases were explained. There, she presented the results obtained in the Smart4Fabry project coordinated by the CIBER-BBN where nanoliposomes were developed for the treatment of Fabry disease. The work, entitled “Preclinical Validation of Nanoliposomes for ERT for Fabry disease”, was a result of the collaboration of the groups of Dr. Ventosa and Dr. Corchero, both from CIBER-BBN, and the participation of units U1, U3, U6, and U20 of the ICTS Nanbiosis.

In addition, today Dr. Abasolo participated in the Nano Rare Day session, organized by the NanoMedSpain platform and the Barcelona Bioengineering Institute (IBEC) at the Sant Joan de Deu Hospital in Barcelona, presented the work entitled “Use of natural and artificial nanoparticles for the treatment of lysosomal storage diseases”, where in addition to nanoliposomes, she also detailed how extracellular vesicles can be a good vehicle to improve replacement enzyme therapy in lysosomal diseases.

Also Dr. Juan Pablo Salvador from NANBIOSIS U2 CAbS has presented at in the Nano Rare Day session his talk on “Quorum Sensing to improve the management of cysticfibrosis“, explaining the difficulty of quickly identifying bacterial infections, which are common in patients with Cystic Fibrosis. In this sense, “Quorum Sensing”, a microbial communication mechanism through which the cells themselves regulate the expression of genes based on cell density, can help identify biomarkers and improve the management of cystic fibrosis.

Related news: Fabry Desease in the Rare Disease Day: A New Hope

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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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