Predictions indicate an increase up to 21.6 million cases of cancer every year by 2030, making it the leading cause of death worldwide. World Cancer Research Day exists as a reminder of the relevance of research that focuses on facing this issue, increasing social awareness, promoting international collaboration, and bringing together all the organizations, centers, and world health leaders that are doing research towards the goal of improving our response to cancer.
Inside many institutions, there are departments that are utilizing their knowledge and expertise to help improve the processes and results related to the detection, diagnosis and treatment of cancer. That is the case for some ICMAB Groups.
Three different departments are working on this issue within the context of a specific Research Line as part of the FUNFUTURE program: Research Line 5: BIOACTIVE MATERIALS FOR THERAPY & DIAGNOSIS (THERANOSTICS).
Facing cancer with nanocapsules and high radioactivity
While radioactivity is already used in cancer therapy and imaging, the process still allows for a lot of improvement. As it stands, radiotherapy is a very aggressive process with a lot of negative side effects.
A new way to improve radiotherapy is being developed by ICMAB Researchers at the Solid State Chemistry (SSC) Group, together with the Catalan Institute of Nanoscience and Nanotechnology (ICN2) and other research centers and universities in the United Kingdom (King's College London, Queen Mary University of London), France (University of Strasbourg), Greece (University of Ioannina Medical School), Czech Republic (Czech Technical University, J. Heyrovsky Institute of the Physical Chemistry,) and Italy (University of Trieste), and a French company (Cis Bio International). The project also appears in the context of the NEST ERC, which funds this research under the Horizon 2020 framework.
Fig. 1. Neutron activation of element in a nanocapsule (SSC)
The process, which has already been tested in vivo experiments with mice, consists of using carbon nanocapsules filled with stable materials that are irradiated, to a high level of radioactivity, right before entering the body. The capsules are made of rolled and sealed up graphene, filled with samarium atoms (samarium chloride), already used as a palliative for bone metastases. When irradiated with neutrons, the stable 152 isotopes become radioactive 153 isotopes useful for cancer treatment.
There are many benefits to this process. A lot of them stem from the fact that the samarium is not radioactive during handling, making it safer for researcher’s who have to take less exposure to radioactive materials during construction, which can happen in any lab, even if it is not equipped for work with radiation. It also makes the capsule last longer: since the material is not activated until it’s used, it can be stored for much longer. Once activated, the high level of radioactivity achieved allows the dose administered to be much lower than with other treatments.
The nanocapsules used to store the samarium atoms are a key element of this process. ICMAB Researcher Gerard Tobías indicates that the nanocapsules are "impermeable, as the graphene wall does not allow the radioactive atoms inside to spread to the rest of the body”. They are also biocompatible, which makes them safe to use in the context of medicine and healthcare.
“More studies still need to be done to calculate optimal doses and side effects, but the existing results are very promising", explains Gerard Tobías.
Nanocarriers for theranostics: targeting cancerous tissue
Another way to limit the negative effects of cancer therapy and diagnosis (theranostic) is to find a way to only affect tumorous cells. Researchers at the Inorganic Materials & Catalysis (LMI) Group are working on the development of multifunctional hybrid nanocarriers that target tumour tissue and can be used for different diagnosis methods as well as for multimodal therapies. This is a faster way to attack cancerous cells that also has less negative effects.
Their research focuses on the development of anticancer agents for BNCT, a process “based on the large capture neutrons surface of 10B, is a promising binary therapy treatment form of radiotherapy, which exploits the potential of some specific isotopes, such as boron-10, to capture thermal neutrons producing energetic α particles suitable for the treatment of cancer, because malignant cells can be selectively targeted and destroyed”, according to ICMAB Researcher Clara Viñas. “The group has developed several strategies to prepare boron-enriched materials using boron clusters that consists on their attachment onto nanocarriers, such as dendrimers, polymers, nanoparticles, among others, leading to payloads with a high boron density. Parallel to their use as BNCT agents, boron clusters have been found to be very good scaffolds for diagnostic and therapeutic labelling, opening the door to a wide range of biomedical applications”.
Fig. 2. Schematic representation of the “in vitro” (with glioblastoma cells) and “in vivo” boron containing drug studies (LMI)
More specifically, the group develops “boron-rich multifunctional biomaterials for BNCT: metallacarborane/proteins, nucleic acids and DNA, nanohybrids (carboranyl + anilinoquinazolines) and nanoparticles as vehicles of cancer drugs or as anticancer drugs that, exhibiting desirable in vitro antitumor activities, open the possibility to be used for multimodal treatments”. The focus on selective NP drug carriers allows nanohybrids and nanoparticles to be used for both diagnosis and treatment.
“The improvements in particles technology, the advances in medical imaging and computing and the fact that new irradiation facilities are becoming available at hospitals, makes radiotherapies such as BNCT, that requires thermal neutrons, a viable choice for cancer medical therapy especially indicated for tumours resistant to chemotherapy and radiotherapy. […] All these evidences promise to make BNCT a cutting-edge technology readily more accessible.”
Improving Adoptive Cellular Therapy with hydrogel scaffolds
A particular challenge in cancer therapy is the design of processes that can engage cancerous cells without damaging the rest of the body, since a lot of the current methodologies have several undesirable side effects. One of the fields trying to face this issue is immunotherapy, a medical strategy that tries to reinforce the body’s own mechanisms to cure cancer, making it a very unobtrusive process compared to others.
Within immunotherapy, there is the branch of Adoptive Cellular Therapy, which has already found success in some advanced blood cancer cases. This kind of therapy reinforces and multiplies T Cells, which are the kind of cell in the body that is able to combat cancerous cells, in order to increase the chances of success against the disease. However, this process still has limitations, like the difficulty to farm enough T cells in an economically viable way and in a short enough period of time.
In order to improve this issue, Researchers at the Max Planck Partner Group “Dynamic Biomimetics for Cancer Immunotherapy” within the Molecular Nanoscience and Organic Materials (NANOMOL) Group are working on ways to improve the harvesting of T Cells. They are doing so by accounting for the ways in which lymph nodes affect the growth of these cells. ICMAB Researcher Judith Guasch affirms: “Our research group has proven the importance of adding a three-dimensional (3D) scaffold into the standard T cell cultures”.
Fig. 3. 3D hydrogels for immunotherapy (Nanomol)
While the current process harvests T Cells expanded in suspension, usually using artificial antigen presenting cells, ICMAB Researchers have been creating 3D structures around which T Cells present a faster growth: “we observed higher T cell proliferation rates than in the state-of-the-art methodologies, which encouraged us to further develop 3D systems especially designed to mimic the lymph nodes in the laboratory. With this objective, we have recently described the use of hydrogels consisting of polyethylene glycol (PEG) and heparin, which not only improve T cell proliferation, but also modify the phenotype of the obtained cells. In these 3D systems, the PEG, a biocompatible polymer widely used in biomedicine, provides the needed structural and mechanical properties, whereas the heparin, a known anticoagulant agent, is used to introduce biochemical stimuli”.
Their research is taking several directions in order to more successfully mimic lymph nodes, like the optimization of the hydrogel’s structure, or the creation of a microfluidic system towards the fabrication of an organ-on-a-chip, which would have more uses besides T Cell harvesting, including the use as artificial testing systems to test drugs in biomedical research laboratories without using live animals, further improving the research process.
While facing cancer is a complex issue, the research of these ICMAB Groups will join other national and international efforts in order to give health professionals stronger and well-suited tools to stand up to it.
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