Cancer is one of the most relevant diseases worldwide because of its incidence, prevalence and mortality. During the past decades, considerable efforts have been devoted to understand the origin of the disease, find early detection methods that could improve the survival rate of cancer patients or develop treatments and devices that could reduce or eradicate cancer. The application of nanotechnology for the rational design of biomaterials is providing alternative solutions to classical treatments, thus expanding the toolbox available for biomedical imaging and therapy. Nanomaterials offer a unique platform to adjust essential properties such as solubility, diffusivity, blood-circulation half-life, pharmacokinetic profile and cytotoxicity. Nanoencapsulation of biomedically relevant payloads into porous materials is of special interest for the development of contrast agents and smart therapeutic systems. Most of our research activity is in the area of nanooncology, by developing nanomaterials for both diagnosis and treatment of cancer in the framework of the ERC Consolidator Grant NEST.
From the wide range of nanomaterials available, our focus is on the exploitation of the unique properties that both, carbon and inorganic nanomaterials offer. When combined, the synergies of both types of materials results in novel or enhanced properties that are of interest not only in the biomedical field but also in other research areas as highlighted below.
We have developed radioactive nanocapsules that allow nuclear imaging in an ultrasensitive manner and lung cancer therapy. Two different strategies have been employed for the preparation of ‘hot’ radioactive nanocapsules. The first strategy consists in the direct encapsulation of radionuclides in their cavities of the carbon nanocapsules. The second strategy goes via the initial encapsulation of a ‘cold’ isotopically enriched isotope (152Sm), which can then be activated on demand to their ‘hot’ radioactive form (153Sm) by neutron irradiation. The use of ‘cold’ isotopes avoids the need for radioactive facilities during the preparation of the nanocapsules, reduces radiation exposure to personnel, prevents the generation of nuclear waste, and evades the time constraints imposed by the decay of radionuclides. A high specific radioactivity (up to 11.37 GBq/mg) has been achieved by neutron irradiation, making the “hot” nanocapsules useful not only for in vivo imaging but also therapeutically effective against lung cancer metastases after intravenous injection. The external surface remains available and can be funtionalized to increase the dispersability, biocompatibility and for targeting purposes. Glycans, peptides and antibodies have been employed in the performed studies. The high in vivo stability of the radioactive payload, selective toxicity to cancerous tissues, and the elegant preparation method offer a paradigm for application of nanomaterials in radiotherapy.
Neutron capture therapy (NCT) is a high-linear energy transfer form of radiotherapy that exploits the potential of some specific isotopes for cancer treatment, based on the neutron capture and emission of short-range charged particles, which occur at low energies. The nuclear reaction that takes place when some isotopes are irradiated with low-energy thermal neutrons, produces high linear energy transfer (LET) particles suitable for cancer cell eradication. The limited path lengths of the LET particles (5-9 µm) produced in NCT can limit the destructive effects to isotopes that are localized in cells. Thus, conferring high therapeutic precision to this type of radiotherapy. We are developing several nanocarriers with the aim to increase the amount of neutron capture elements that are delivered to cancer cells (patent application 202230271).
Although optical imaging is still the leading imaging modality in laboratory-based biomedical research mainly due to its convenience and low cost, magnetic resonance imaging (MRI) and nuclear imaging are currently the mainstream clinical diagnostic approaches. MRI is already a standard medical imaging technique which offers excellent spatial and temporal resolution, and good soft tissue contrast. In this field, we have combined the outstanding properties of superparamagnetic iron oxide nanoparticles (SPION) as positive contrast agents for MRI along with those of carbon nanomaterials, namely graphene and carbon nanotubes that are employed as nanocarriers. The resulting hybrid materials offer high r2 relaxivities in both phantom and in vivo MRI compared to clinically approved SPION. We have also shown that not only the characteristics of the SPION but also the employed nanocarrier might play a key role in the resulting properties. For instance, short carbon nanotubes reveal enhanced MRI properties compared to their long counterparts. We are also exploring the contrast imaging properties of 3D scaffolds of graphene oxide (using a patented technology, WO 2019/158794 A1) bearing SPION.