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Advanced Radiotherapy, Generated by Exploiting Nanoprocesses and Technologies

Final Report Summary - ARGENT (Advanced Radiotherapy, Generated by Exploiting Nanoprocesses and Technologies)

Introduction & project objectives:
Cancer remains a major European health concern. Around 50% of patients receive radiotherapy as part of their cancer treatment. The main limitation of this treatment is the lack of tumour selectivity,which causes severe side effects, and radioresistance. New promising strategies are proposed, which are based on the use of innovative sources such as particle therapy (carbon therapy and protontherapy) and/or on concomitant addition of nanoparticles.
The ARGENT project (http://itn-argent.eu/) brought together World-leading researchers of different disciplines, physicists and medical physicists, chemists, biologists, medical doctors together with industrials with the aim of exploring the underpinning processes together with potential routes of clinic translation. This European effort aimed at developing and optimizing new nanodrugs and advanced radiation protocols.
Another objective was to train a new generation of supra-disciplinary experts in hot scientific and innovation developments such as new medical physics techniques, nanosciences and material sciences for radiation therapies, biology under radiation, ready to enter academic sector or private companies.
Last but not least, it was an important issue to train these young researchers to not only develop world-wide innovative methods for cancer treatments but also to become ambassadors and promote European expertise and know-how .

Main achievements
A full characterization of the nanoscale processes involved in the action of nanoparticles when combined with radiation therapies is now possible . This is achieved thanks to i) the finalization of a new software to perform molecular dynamics simulation of metallic nanoparticles, the construction of a new setup able to measure fundamental characteristics (cross sections, stopping power and energy loss values) of radiation sources, iii) an apparatus installed on a big instruments (GANIL) dedicated to the production and fundamental analysis of nanoparticles interacting with an incident beam of high-energy ions have been settled.
In parallel, therapeutic nanoagents have been developed and tested in vitro. Thus platinum based nanoagents able to amplify particle beam effects, not toxic have been produced using original and efficient method patent is in progress. The efficiency of nanoparticles to amplify radiation effect in hypoxia environments (responsible for radioresistance) has been proved. It confirms the need to improve understanding of the amplification phenomenon with the aim to design best nanoagents. In addition, new antibodies have been successfully produced with the properties to improve tumor targeting of nano drugs when coated with these agents. Finally a new route to scale up the production of the highly promising AGuiX compound has been achieved, which opens the possibility for this compound to be transferred to the clinic (currently in progress).

The installation in a hospital of a radiation detector for the acquisition of comprehensive dataset has optimized the measurements of nanodosimetry measurements.
The data have been utilized as inputs for simulations with potential transfer to treatment planing (TPS). In parallel, simulations of tracks including effect of water radicals for the case of high-energy ion treatments have been performed. The model has been tested by performing measurements with a ion medical beam, thanks to the partnership with hadrontherapy centers. Finally, the radiosensitisation/radio-enhancement properties of several nanoagents composed of gold, platinum or gadolinium have been demonstrated on human cancer lines.

Impact
A new generation of 13 ESRs will continue to generate new data, models and strategies for the future developments of advanced radiation therapies and nanotechnologies for cancer treatment.
A new set of potential nanodrugs able to improve not only radiation therapies but also diagnosis and tumor targeting, has been delivered. New models and protocols have been optimized.
The level of dissemination (publications and conferences) was high and all the ESRs will obtain PhDs. Two newsletters have been launched and the website has been updated. An international conference ended the project. So most of the results and related outcomes will be accessible to a broad scientific community and to the public.
The projet already impacted the communities related to cancer research and treatment, and other projects are currently in development.

ARGENT project website: http://itn-argent.eu/
Contact: Sandrine Lacombe, ARGENT coordinator, ISMO lab (CNRS – Université Paris Sud)
sandrine.lacombe@u-psud.fr