News U20

Temperature-sensitive hydrogels: A pioneering therapeutic approach for ovarian cancer

A new project with the participation of NANBIOSIS Unit 20 pioneers thermosensitive hydrogels for localized ovarian cancer treatment, minimizing side effects and enhancing efficacy.

May 2024, VHIR/FVPR/CIBER-BBN (Barcelona). As the world recently commemorated Ovarian Cancer Day, from NANBIOSIS we proudly highlight the groundbreaking work of our collaborators in the fight against this deadly disease. Ovarian cancer stands as the seventh leading cause of cancer-related deaths, with Europe bearing the brunt of its impact, recording over 44,000 fatalities annually.

In a bid to revolutionize treatment paradigms and enhance patient outcomes, researchers at the Clinical Biochemistry, Drug Delivery and Therapy (CB-DDT) Group, in close collaboration with NANBIOSIS Unit 20, are spearheading an innovative project focused on intraperitoneal drug delivery for ovarian cancer.

Traditionally, ovarian cancer treatment has been marred by the limitations of systemic chemotherapy, often leading to severe toxicities and treatment resistance. To address these challenges, the team led by Dr. Diana Rafael has embarked on developing a novel therapeutic approach using thermosensitive hydrogels (HG) for sustained intraperitoneal drug release.

By utilizing temperature-sensitive hydrogels, our researchers can deliver chemotherapeutic agents directly to the abdominal cavity, minimizing systemic side effects and enhancing therapeutic efficacy.

As explained by Dr. Rafael, this project aims to provide a new, localized treatment strategy for ovarian cancer patients. In this regard, the group’s multidisciplinary expertise spans pharmaceutical technology, nanomedicine, and cancer biology. Thus, by utilizing temperature-sensitive hydrogels, our researchers can deliver chemotherapeutic agents directly to the abdominal cavity, minimizing systemic side effects and enhancing therapeutic efficacy.

About the project:

The two funding sources, aptly named SmartTheC and HydroTheC, are granted by the La Caixa Foundation and the European Commission, respectively. It focuses on the development of eco-friendly and biodegradable hydrogels capable of prolonged drug release, thereby reducing the need for repeated treatments and improving patient quality of life. These HG are liquid at room temperature, facilitating their administration, and then turn into a gel upon exposure to the body temperature.

One of the key innovations of this approach lies in the incorporation of nanoparticles within the hydrogel matrix, enabling a “multi-compartment” system capable of releasing different drugs at varying rates.

One of the key innovations of this approach lies in the incorporation of nanoparticles within the hydrogel matrix, enabling a “multi-compartment” system capable of releasing different drugs at varying rates. This versatility is crucial for personalized treatment regimens and overcoming drug resistance.

The aim is to significantly enhance the therapeutic window of drugs and improve patient survival. Moreover, the biodegradability and extended residence time of the formulation offer distinct advantages over existing treatment options, paving the way for easy translation to clinical application.

The project’s preclinical validation phase, which includes in vivo experiments utilizing advanced cancer models established by our Unit 20, is being conducted in close collaboration with specialist ovarian cancer physicians from HUVH, ensuring alignment with patient needs and clinical realities.

The culmination of these efforts promises not only improved outcomes for ovarian cancer patients but also significant reductions in healthcare costs associated with treatment. Finally, this approach could be easily adapted to many other existing treatments that require local administration thanks to its versatility and easy adaptation.

Funding of the project:

SmarTheC: “Eco-sustainable Smart Hydrogels for the Sustained Intraperitoneal Release of Chemotherapeutics as a Novel Local Therapy Approach for Advanced Ovarian Cancer” (143178), La Caixa Foundation (Starting on 31/12/2024), Principal Investigator: Diana Rafael

HydroTheC: Biodegradable and Eco-friendly Smart Hydrogels for the Sustained Intraperitoneal Release of Chemotherapeutics as a Novel Local Therapy Approach for Advanced Ovarian Cancer” (101107735), Global MSCA-PF Granted to: Diana Rafael, European Commission.

About 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, 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:

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:

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.

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:

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: