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Nanocapsules for targeted delivery of radioactivity

Final Report Summary - RADDEL (Nanocapsules for targeted delivery of radioactivity)

RADDEL is an inter-sectorial European network formed by 11 partners from 7 different countries that was awarded by the European Commission with a Marie Curie Initial Training Network (ITN) grant under the EU´s FP7 PEOPLE program. The network is formed by leading experts from Universities, Research Centers and Industry willing to share their complementary expertise, infrastructure and facilities for the training of the next generation of top-quality researchers through the development of new science. The project has been coordinated by Dr. Gerard Tobias (ICMAB-CSIC, Spain) and has involved the following partners: Prof. Benjamin G. Davis (Univesity of Oxford, UK), Prof. Kostas Kostarelos (University of Manchester, UK), Dr. Khuloud Al-Jamal (King’s College London, UK), Prof. Maurizio Prato and Prof. Tatiana Da Ros (Universita Degli Studi di Trieste, Italy), Dr. Alberto Bianco (CNRS, Strasbourg), Dr. Belén Ballesteros (Catalan Institute of Nanoscience and Nanotechnology, Spain), Dr. Dimitris Emfietzoglou (University of Ioannina, Greece), Dr. Martin Kalbác (Ustav Fyzikalni Chemie J. Heyrovskeho, Czech Republic), Dr. Jean-Claude Saccavini (Cis Bio International-Ion Beam Applications SA, France) and Prof. Gustaaf Van Tendeloo (EMAT-University of Antwerp, Belgium). RADDEL started in February 2012 and finished in January 2016.

The network has recruited 20 young scientists that have been the driving force of RADDEL, namely 14 Early Stage Researchers and 6 Experienced Researchers. A well structured training program has been provided to them with a balanced combination of local and network-wide training through secondments, joint network meetings, workshops, schools, industrial training and a final network conference.

While the training program has been designed to provide the Fellows with the necessary expertise to improve their research skills and enhance their career prospects, the scientific program has aimed at developing novel nanomaterials for biomedical applications. In particular, over these four years the project has focused on the design, synthesis, characterization, pharmacological studies and dosimetry calculations of nanocapsules that contain in their interior radioactive materials for biomedical applications in the areas of cancer diagnosis and therapy. After filling the selected radionuclides, the external walls of the nanocapsules have been decorated with a wide variety of biomolecules to render them biocompatible and for targeting purposes.

Several key aspects have been addressed during the course of the Project to move the “nanocapsules” (filled carbon nanotubes) closer to the clinic. The industrial partner has played a key role ensuring that the selected payloads were clinically relevant for their translation in use with humans. Within the consortium we have achieved the encapsulation of several radionuclides of interest for an early diagnosis and more personalized treatment of cancer. A specific Monte Carlo simulation code has been developed to perform dosimetry calculations of the prepared constructs. Once the nanotubes have been filled, a wide variety of protocols have been developed to afford the covalent functionalization of their walls whilst preserving the encapsulated compounds. This has required the use of mild strategies that do not damage the structure of the nanotubes. If structural holes were present on the walls of the nanocapsules, this would result in leakage of the encapsulated materials in vivo. Further derivatization of initially anchored functional moieties has also been carried out to attach targeting moieties which include the use of a library of carbohydrates, peptides and antibodies. In this sense, remarkable has been the specific targeting not only of cancer cells but even of cellular organelles after the internalization of the nanocapsules. The developed radioactive nanocapsules have shown an excellent performance in vivo. The prepared constructs have been properly characterized at all the different stages by top leading partners in electron microscopy and spectroscopy. The scientific results of the research program can be found in the publication list available at the project’s webpage: http://projects.icmab.es/raddel/.

The achievements of the network have been spread to both the scientific community and the general public through several dissemination and outreach activities that have taken place during these four years. The scientific community has mainly been reached via presentation of the research results at well established international conferences and publication in high impact peer-reviewed journals. Among the different dissemination and outreach activities, worth mentioning are the final network conference and a recent press release that has attracted the interest of mass media channels.

The conference, entitled "Latest advances on nanomaterials for biomedical applications" (NANOBIOAPP2015) was held in Barcelona (Spain) on the 21st-23rd September 2015. The scope of the conference was to bring together experts not only in the field of carbon nanomaterials but also on other types of nanomaterials to create a suitable environment for an interdisciplinary discussion of the latest advances in the biomedical field. Keynote and invited speakers for the conference were top worldwide leading scientists, some of them being the Scientists-in-Charge of RADDEL. Their expertise ranged from the synthesis and characterization of the nanomaterials up to their in-vivo application. The conference was an excellent opportunity for the Fellows to present their results. A specific session was devoted to the RADDEL project and all the Fellows delivered an oral talk to the audience. The conference was a great success with over 100 participants attending from across Europe and overseas. Further information can be found at the webpage of the event: http://congresses.icmab.es/nanobioapp2015/

The press release, entitled “A novel targeted anticancer therapy system based on carbon nanocapsules”, attracted the interest of mass media channels, including well established national newspapers such as La Vanguardia in Spain or El Universal in Mexico, as well as several social networks.

Overall, RADDEL has gone beyond the state-of-the-art in the field of cancer diagnosis and therapy, developing innovative products and solutions which in the long term might have a high socio-economic impact in this fast evolving field. From a training perspective, the young researchers have been able to develop their own career path benefiting from an interdisciplinary and intersectoral training. The success of the RADDEL training program becomes patent by looking at the career perspectives of the Fellows. Several of them have already moved to the next step, which includes postdoctoral positions at well established institutions (ESRs) and even permanent positions at recognized Universities (ERs).