Nanoengineering of carbon and inorganic materials (NanoCIM)

Led by: Dr. Gerard Tobías Rossell

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.

Contact

gerard.tobias@icmab.es
Dr. Gerard Tobías Rossell

Research Highlights


NANOONCOLOGY

Theragnostic nanocapsules – nuclear medicine

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

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).

Magnetic resonance imaging

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.

LOW DIMENSIONAL SYSTEMS

1D tubular van der Waals heterostructures

The electronic and optical properties of two-dimensional layered materials allow the miniaturization of nanoelectronic and optoelectronic devices in a competitive manner. Even larger opportunities arise when two or more layers of different materials are combined. We have observed that the cavities of carbon nanotubes can be employed for the template assisted growth of inorganic metal halide nanotubes in their interior, thus forming 1D tubular van der waals heterostructures. We have developed strategies that result in a high selectivity toward the growth of such 1D heterostructures. A decrease of the resistivity as well as a significant increase in the current flow upon illumination has been observed in a PbI2@CNT bulk matrix. Both effects are attributed to the presence of single-walled lead iodide nanotubes in the cavities of carbon nanotubes (CNTs), which dominate the properties of the whole matrix.

Research Projects


Engineering complex inorganic materials for energy aplications, ECIME
Ministerio de Ciencia e Innovación, 2022-2024. IP: A. Fuertes, G.Tobías
Nanoengineering of radioactive seeds for cancer therapy and diagnosis NEST
ERC Consolidator Grant, 2016-2022. IP: G. Tobías
Graphene reinforce composites for 3D printing technology 3D-PRINTGRAPH
MSC-IF, 2016-2020. IP: G. Tobías
Boron enriched carbon nanomaterials as theranostic agents for biomedical imaging and BNCT, BECMATA
SO-FUNMAT-FIP, 2017-2018. IP: R. Núñez, G.Tobias
Development of ultra-sensitive nanotherapeutic anticancer agents for boron neutron capture therapy, NANOTER
MSC-IF, 2016-2018. IP: G. Tobías
Nanocapsules for Targeted Delivery of Radioactivity, RADDEL
ITN, 2012-2016. Network Coordinator and IP: G. Tobías. 

Partnerships for Technology Transfer


Books and book chapters


Nanooncology

Gil Gonçalves and Gerard Tobias (Editors)
Nanooncology: Engineering nanomaterials for cancer therapy and diagnosis
(Springer, 2018). ISBN: 978-3319898773.

Gerard Tobias, Emmanuel Flahaut
Smart carbon nanotubes 
Smart materials for drug delivery (Royal Society of Chemistry)
Vol. 2, p. 90-116 (2013). ISBN: 978-1-84973-552-0.

Gerard Tobias, Ernest Mendoza, Belén Ballesteros
Functionalisation of carbon nanotubes 
Encyclopedia of Nanotechnology (Springer) 
Part 7, 911-919 (2012). ISBN: 978-90-481-9750-7.

Selected Publications


Theragnostic nanocapsules

Functionalization of filled radioactive multi-walled carbon nanocapsules by arylation reaction forin vivodelivery of radio-therapy
Gajewska A., Wang J.T., Klippstein R., Martincic M., Pach E., Feldman R., Saccavini J.-C., Tobias G., Ballesteros B., Al-Jamal K.T., Da Ros T., 
J. Mater. Chem. B.  2022, 10 (1), 47-56

Neutron-irradiated antibody-functionalised carbon nanocapsules for targeted cancer radiotherapy
Wang J.T.-W., Spinato C., Klippstein R., Costa P.M., Martincic M., Pach E., Ruiz de Garibay A.P., Ménard-Moyon C., Feldman R., Michel Y., Šefl M., Kyriakou I., Emfietzoglou D., Saccavini J.-C., Ballesteros B., Tobias G., Bianco A., Al-Jamal K.T.
Carbon.  2020, 162, 410-422

Neutron Activated 153Sm Sealed in Carbon Nanocapsules for in Vivo Imaging and Tumor Radiotherapy
Wang J.T.-W., Klippstein R., Martincic M., Pach E., Feldman R., Šefl M., Michel Y., Asker D., Sosabowski J.K., Kalbac M., Da Ros T., Ménard-Moyon C., Bianco A., Kyriakou I., Emfietzoglou D., Saccavini J.-C., Ballesteros B., Al-Jamal K.T., Tobias G.
ACS Nano.  2020, 14 (1) 129-141

In vivo behaviour of glyco-NaI@SWCNT ‘nanobottles’
De Munari S., Sandoval S., Pach E., Ballesteros B., Tobias G., Anthony D.C., Davis B.G.,
Inorg. Chim. Acta.  2019, 495, 118933

Non-cytotoxic carbon nanocapsules synthesized via one-pot filling and end-closing of multi-walled carbon nanotubes
Martincic M., Vranic S., Pach E., Sandoval S., Ballesteros B., Kostarelos K., Tobias G.
Carbon  2019, 141, 782-793

Evaluation of the immunological profile of antibody-functionalized metal-filled single-walled carbon nanocapsules for targeted radiotherapy
Perez Ruiz De Garibay A., Spinato C., Klippstein R., Bourgognon M., Martincic M., Pach E., Ballesteros B., Ménard-Moyon C., Al-Jamal K.T., Tobias G., Bianco A.
Sci. Rep.  2017, 7, 42605 

Carbon nanotubes allow capture of krypton, barium and lead for multichannel biological X-ray fluorescence imaging
Serpell C.J., Rutte R.N., Geraki K., Pach E., Martincic M., Kierkowicz M., De Munari S., Wals K., Raj R., Ballesteros B., Tobias G., Anthony D.C., Davis B.G.
Nat. Commun.  2016, 7, 13118

Design of antibody-functionalized carbon nanotubes filled with radioactivable metals towards a targeted anticancer therapy
Spinato C., Perez Ruiz De Garibay A., Kierkowicz M., Pach E., Martincic M., Klippstein R., Bourgognon M., Wang J.T.-W., Ménard-Moyon C., Al-Jamal K.T., Ballesteros B., Tobias G., Bianco A.
Nanoscale.  2016, 8 (25), 12626-12638

Filled and glycosylated carbon nanotubes for in vivo radioemitter localization and imaging. Hong S.Y.
Tobias G., Al-Jamal K.T., Ballesteros B., Ali-Boucetta H., Lozano-Perez S., Nellist P.D., Sim R.B., Finucane C., Mather S.J., Green M.L.H., Kostarelos K., Davis B.G.
Nat. Mater.  2010, 9 (6), 485-490   

Magnetic resonance imaging

Green and Solvent-Free Supercritical CO2-Assisted Production of Superparamagnetic Graphene Oxide Aerogels: Application as a Superior Contrast Agent in MRI
Borrás A., Fraile J., Rosado A., Marbán G., Tobias G., López-Periago A.M., Domingo C.
ACS Sustainable Chem. Eng.  2020, 8 (12), 4877-4888 

Particle size determination from magnetization curves in reduced graphene oxide decorated with monodispersed superparamagnetic iron oxide nanoparticles
Bertran A., Sandoval S., Oró-Solé J., Sánchez À., Tobias G.
J. Colloid Interface Sci.  2020, 566, 107-119 

Microwave-assisted synthesis of SPION-reduced graphene oxide hybrids for magnetic resonance imaging (MRI)
Llenas M., Sandoval S., Costa P.M., Oró-Solé J., Lope-Piedrafita S., Ballesteros B., Al-Jamal K.T., Tobias G.
Nanomaterials.  2019, 9 (10), 1364

Novel Fe3O4@GNF@SiO2 nanocapsules fabricated through the combination of an: In situ formation method and SiO2 coating process for magnetic resonance imaging
Lu C., Sandoval S., Puig T., Obradors X., Tobias G., Ros J., Ricart S.
RSC Adv.  2017, 7  (40), 24690-24697

The Shortening of MWNT-SPION Hybrids by Steam Treatment Improves Their Magnetic Resonance Imaging Properties in Vitro and in Vivo
Wang J.T.-W., Cabana L., Bourgognon M., Kafa H., Protti A., Venner K., Shah A.M., Sosabowski J.K., Mather S.J., Roig A., Ke X., Van Tendeloo G., De Rosales R.T.M., Tobias G., Al-Jamal K.T.
Small.  2016, 12 (21), 2893-2905 

Magnetically decorated multiwalled carbon nanotubes as dual MRI and SPECT contrast agents
Cabana L., Bourgognon M., Wang J.T.-W., Protti A., Klippstein R., De Rosales R.T.M., Shah A.M., Fontcuberta J., Tobías-Rossell E., Sosabowski J.K., Al-Jamal K.T., Tobias G.
Adv. Funct. Mater.  2014, 24 (13), 1880-1894

 

1D tubular van der Waals heterostructures

Structure of inorganic nanocrystals confined within carbon nanotubes
Sandoval S., Tobias G., Flahaut E.
Inorg. Chim. Acta.  2019, 492, 66-75   

Selective Laser-Assisted Synthesis of Tubular van der Waals Heterostructures of Single-Layered PbI2 within Carbon Nanotubes Exhibiting Carrier Photogeneration
Sandoval S., Kepić D., Pérez Del Pino Á., György E., Gómez A., Pfannmoeller M., Tendeloo G.V., Ballesteros B., Tobias G.
ACS Nano.  2018, 12 (7), 6648-6656 

Encapsulation of two-dimensional materials inside carbon nanotubes: Towards an enhanced synthesis of single-layered metal halides
Sandoval S., Pach E., Ballesteros B., Tobias G.
Carbon.  2017, 123, 129-134

Synthesis of PbI2 single-layered inorganic nanotubes encapsulated within carbon nanotubes
Cabana L., Ballesteros B., Batista E., Magén C., Arenal R., Orõ-Solé J., Rurali R., Tobias G.
Adv. Mater.  2014, 26 (13), 2016-2021

Contact

Address

  • ICMAB-CSIC
    Campus de la UAB
    08193 Bellaterra