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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:

Last seat: Our Training in Spectroscopy and MRI for animal testing applications is still open.

Do not miss the chance to join our hands-on XV Workshop of Theoretical-Practical Training in MRS / MRI, with specific application in laboratory animals

Our excellent teacher Dr. Silvia Lope will be at the helm in this practical workshop. And it provides all the required skills users need to operate our fantastic Biospec, available as a service in our Unit 25.

The registration period for the “XV Workshop of Theoretical-Practical Training in Spectroscopy and Magnetic Resonance Imaging (MRS / MRI): Application in Laboratory Animals” is still open until May the 17th, 2024. This workshop is organized by the Department of Biochemistry and Molecular Biology and the Nuclear Magnetic Resonance Service of the Autonomous University of Barcelona, and will take place from May 28 to 30, 2024.

The aim of this workshop is to serve as an introduction to the application of the Magnetic Resonance Imaging (MRI) technique in preclinical studies.

The aim of this workshop is to serve as an introduction to the application of the Magnetic Resonance Imaging (MRI) technique in preclinical studies. The fundamental theoretical concepts that allow understanding the operation of the technique will be explained, with special emphasis on practical application with small animals using our state of the art 7 Teslas Bruker Biospec spectrometer.

The workshop is aimed at students and researchers who want to get started in spectroscopy and magnetic resonance imaging techniques applied to laboratory animals.

How do I apply?

If you are interested, you can download the brochure and the registration form at https://tinyurl.com/XVpreclinicalMRIMRSworkshop. For registration, just submit the registration form back by e-mail to the following address: silvia.lope@uab.cat.

The number of participants is limited to 4 people, and there is one seat left. Do not miss this opportunity!

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:

New cathalitic therapy for destroying key molecules within tumor cells

The prestigious journal Nano Letters published the work led by NANBIOSIS researchers, affiliated with Unizar, INMA (CSIC-UNIZAR), CIBER–BBN, and IIS Aragón.

The successful development of this innovative treatment approach was possible through the efforts of our Unit 9, led by Prof. Santamaría and Dr. Hueso, both corresponding authors of the publication.

As recently announced by Universidad de Zaragoza (Unizar), a team led by NANBIOSIS researchers at the Instituto de Nanociencia y Materiales de Aragón (INMA, a joint institute of CSIC and UNIZAR) has discovered a way to artificially conduct a new chemical reaction, called transamination. This approach can act within cancer cells to destroy molecules vital for the development and growth of tumor cells. The prestigious journal Nano Letters have recently published this work, led by Unizar professors and researchers Javier Bonet–Aletá, José Luis Hueso, and Jesús Santamaría, also affiliated with NANBIOSIS, INMA (CSIC-UNIZAR), CIBER–BBN, and IIS Aragon.

The technique aims to replace current chemotherapy, carrying catalysts that either generate toxic molecules inside the tumor or eliminate molecules it needs to keep growing.

Catalytic therapy constitutes a new strategy in the fight against cancer, aiming to trigger harmful chemical reactions for the tumor. Ultimately, the goal is to replace current chemotherapy by carrying catalysts that either generate toxic molecules inside the tumor or eliminate molecules necessary for its proliferation.

Regarding eliminating key molecules, first published in 2015, catalysts targeted either glucose, an important energy source for cancer cells; or glutathione, an antioxidant that protects tumor cells from highly reactive radical species. The later is partly responsible for these cells’ resistance to chemotherapy treatments. Both glucose and glutathione can be eliminated through oxidation reactions. However, this is especially challenging to apply due to the scarcity of oxygen in the hypoxic tumor environment.

The publication:

This study holds special importance not only because it opens the field to new reactions of interest in oncology, but also because it does so in a process – transamination – that does not require oxygen to occur. This eliminates the main restriction of catalytic therapies. The reaction operates on amino acids, essential components that cells use to produce proteins, and also pyruvate, a small and abundant molecule involved in the main energy acquisition pathway in the cell. The reaction between them reduces the levels of amino acids and pyruvate in cancer cells, leading them to a critical state and halting their expansion and growth.

During transamination, an amino group is exchanged between an amino acid and pyruvate, generating a substance that the cell cannot easily utilize. Our researchers demonstrated this by reacting pyruvate with various amino acids, such as glutamine, aspartic acid, glutamic acid, or glutathione itself. However, transamination has one drawback: it is catalyzed by copper atoms, whose flow through the cell membrane under normal conditions is highly restricted. To overcome this limitation, researchers designed nanoparticles containing this metal, enhancing internalization into tumor cells. Once internalized, the nanoparticle dissolves, releasing copper atoms that act as catalysts in the transamination reaction.

In addition of Dr. José Luis Hueso, and Dr. Jesús Santamaría, other members of Unizar also participated, such as Dr. Javier Martin–Martin from the Department of Organic Chemistry and INMA, and Dr. Miguel Encinas–Giménez, Dr. Ana Martín–Pardillos, and Dr. Pilar Martín–Duque, who are also members of the Aragon Health Research Institute (IIS), as well as Dr. Juan Vicente Alegre Requena, a CSIC scientist at the Institute of Chemical Synthesis and Homogeneous Catalysis, ISQCH, a joint CSIC-UNIZAR institute.

References:

[1] Nanoparticle-Catalyzed Transamination under Tumor Microenvironment Conditions: A Novel Tool to Disrupt the Pool of Amino Acids and GSSG in Cancer Cells. Javier Bonet-Aleta, Juan Vicente Alegre-Requena, Javier Martin-Martin, Miguel Encinas-Gimenez, Ana Martín-Pardillos, Pilar Martín-Duque, Jose L. Hueso, and Jesús Santamaria
Nano Letters, 2024 doi: 10.1021/acs.nanolett.3c04947

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:

Protein-only Materials offer a new hope in colorectal cancer treatment

Breakthrough colorectal cancer treatment unveiled by NANBIOSIS Units promises enhanced precision & efficacy in targeted cancer therapies.

March 2024, UAB/Institut de Recerca Sant Pau/CIBER-BBN (Barcelona)

As we leave World Colorectal Cancer Day 2024 behind, marked on March 31st, there have been significant highlights in cancer treatment, a field in which targeted therapies are playing a crucial role.

In this context, researchers from the Nanobiotechnology team, at the Institut de Biotecnologia i de Biomedicina from Universitat Autònoma de Barcelona, led by Prof. Antonio Villaverde, in collaboration with the Oncogenesis and Antitumor Drugs team led by Prof. Ramón Mangues at Institut de Recerca Sant Pau, have made a significant breakthrough in the treatment of colorectal cancer. Their innovative approach, facilitated by their respective Unit 1 and Unit 18 of NANBIOSIS, promises to revolutionize current treatment methodologies and improve patient outcomes.

“In a clinical context, the use of these materials in the treatment of colorectal cancer should greatly improve the drug’s efficacy and patient comfort while minimizing unwanted side effects.”

Prof. Antonio Villaverde, Strategy Director of Unit 1

“It is important to highlight that such accumulation is more effective than when the protein is administered into the bloodstream. This fact offers a new and unexpected way to ensure high local levels of the drug and better clinical efficacy, avoiding repeated intravenous administration regimens,” explains Prof. Villaverde. “In a clinical context, the use of these materials in the treatment of colorectal cancer should greatly improve the drug’s efficacy and patient comfort while minimizing unwanted side effects.”

The team’s groundbreaking research centers around the development of self-contained protein-only materials at the microscale, capable of delivering therapeutic polypeptides in a time-prolonged manner. These materials, resembling the organization of secretory granules within the human endocrine system, are engineered to release functional polypeptide nanoparticles. These nanoparticles can selectively target tumors and destroy specific types of cancer cells, offering a promising avenue for more effective and precise cancer treatment.

The publication:

Notably, the researchers thorougly explored the molecular structure and dynamics of the secretion process of these materials, both in vitro and in vivo. In preclinical trials using an animal model of colorectal cancer, the system demonstrated remarkable efficacy upon subcutaneous administration. This was thanks to the released protein nanoparticles accumulating efficiently in tumor tissues. Importantly, this accumulation was found to be more effective than traditional intravenous administration methods, offering a novel strategy to ensure high local drug levels while minimizing systemic side effects.

Furthermore, several competitive research and technology transfer projects supported this research, as well as intramural CIBER-BBN projects. This further highlights the importance of interdisciplinary collaboration and funding initiatives in driving scientific progress.

The team’s work underscores the importance of continued investment in research and collaboration to tackle the challenges posed by colorectal cancer and other malignancies. As World Colorectal Cancer Day is observed globally, this breakthrough offers hope for a future where innovative treatments pave the way for improved outcomes and enhanced quality of life for cancer patients worldwide.

The successful development of this innovative treatment approach was possible through the collaborative efforts of two NANBIOSIS Units: the Protein Production Platform (Unit 1) and the Nanotoxicology Unit (Unit 18).

References:

[1] J. M. Sánchez, H. López-Laguna, E. Parladé, A. D. Somma, A. L. Livieri, P. Álamo, R. Mangues, U. Unzueta, A. Villaverde, E. Vázquez, Structural Stabilization of Clinically Oriented Oligomeric Proteins During their Transit through Synthetic Secretory Amyloids. Adv. Sci. 2024, 2309427. https://doi.org/10.1002/advs.202309427

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: