Community Research and Development Information Service - CORDIS

FP7

ARGENT Report Summary

Project ID: 608163
Funded under: FP7-PEOPLE
Country: France

Periodic Report Summary 1 - 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. The most promising developments to improve the performances of radiation-based therapies is the use of fast ion beam radiation (carbon therapy and protontherapy) and nanoparticles-enhanced therapies.
The ARGENT project (http://itn-argent.eu/) brings together world-leading researchers of different disciplines, physicists and medical physicists, chemists, biologists, medical doctors and SMEs with the aim of understanding and exploiting the nanoscale processes that drive these phenomena. This European effort should lead to the development and optimization of new nanodrugs together with advanced radiation protocols. This will open a new era for radiotherapy with subsequent economic and ‘quality of life’ benefits for the EU population.
In order for Europe to fully exploit its world-lead, a new generation of supra-disciplinary researchers familiar with i) Physics and medical physics: explaining the physical interactions of radiation; ii) Chemistry: describing the chemical processes and methodologies for tailoring nano-agents; iii) Biology: elucidating the effects in vitro and in vivo. This project is strongly supported by the medical community. As an end point, this intersectoral and multi-disciplinary programme will form young researchers and experts able to create a platform on which next generation cancer therapy will be built.

Main achievements

In the first two years of the project, several main scientific achievements have been met. The nanodosimetry panel has progressed thanks to advanced theoretical and experimental studies. New software has been defined (MBN explorer) to perform Molecular dynamics simulation of metallic nanoparticles. Moreover, Molecular Dynamics simulations of DNA molecules in liquid water have been optimized to evaluate the contribution of shock waves to biodiamage and free radical propagation, a new concept in radiation biology. In parallel an experimental setup has been built to establish the database of cross sections, stopping power and energy loss values needed for future modelling. In addition, a beam of complex nanosystems is being developed to measure the electron emission from nanoparticles or metal clusters activated by incident particles.
In parallel, therapeutic nanoagents have been developed and tested. Firstly, Synchrotron Radiation Circular Dichroism (SRCD) measurements have shown that the gadolinium-based any AGuIX, an agent developed by our partner SME Nano-H, does not induce aggregation of blood proteins, a major toxicity issue limiting intravenous injection. The first evaluation of nanoagents developed within the consortium (mostly gold nanoparticles developed in collaboration with CheMatech and platinum nanoparticles developed at CNRS) have been tested using clinical carbon irradiation. The irradiations have been performed in the two leadership medical centers of Chiba, Japan and our associate partner HIT, Heidelberg, Germany. It has been shown that the uptake dynamics of gold nanoparticles (DTDTPA-Cyanine) depends on the tumour cell line, which sheds the light on the complexity of combining nanoparticles uptake and radiation. The design of nanoparticles has been improved. In particular new coatings containing cancer-targeting immunoglobulins are being developed. Moreover a new synthesis of AGuiX incorporating different metals and functionalization strategies is in progress.
Preclinical evaluation has started with the installation in a hospital of a radiation detector for nanodosimetry measurements. Associated simulations using Monte-Carlo-LEPTS dose deposition in water have been performed. A comprehensive dataset of integral and differential cross sections of elastic and inelastic scattering of low-energy protons from water molecules has been created. These cross sections have then been utilized as input data for the track structure Monte Carlo simulations performed within the LEPTS code. In parallel, using the GSI track structure code (TRAX), simulations of ion tracks including effect of water radicals have been performed. For comparison with this model, survival probability for different cell lines irradiated by different ion beams has been evaluated. The effect of nanoparticles on this effect is still in progress. Finally, the radiosensitisation properties of gold nanoparticles coated with gadolinium have been characterised in normal and cancer prostate models using DNA immunostaining and cell survival, and in vivo experiments will be performed to evaluate models and advanced nano-agents.

Expected results and potential impact

ARGENT is training the next generation of researchers with advanced skills for the development and exploitation of new nanoscience in radiotherapy and healthcare. These 13 ESRs have generated new data and models for the future application of advanced radiotherapies and nanotechnologies. They have received key training on the multidisciplinary areas underpinning their research at Universite Paris Saclay, management and entrepreneurship at a summer school on Science Management for Scientists and Engineers in Geneva and outreach and dissemination training from one of our SME partners (Minerva). Already 10 key publications have been produced and oral and poster presentations delivered at National and International Conferences. A website and newsletters have been launched by the ESRs to publicise their work (www.itn-argent.eu). The wider public has also been engaged during outreach events ranging from talking about science to primary school children to educating PhD students and researchers in other scientific areas. Fundamentally, the next generation of nanoparticle agents and advanced radiotherapy combinations are being developed.
At the end, the projet is expected to impact the community of radiotherapy with new tools (nanoagents and software) and new concepts (nanodosimetry, combined strategy) that will improve the performance of cancer treatment and related devlopments.

Argent project website: http://itn-argent.eu/

Contact: Sandrine Lacombe, ARGENT coordinator, ISMO lab (CNRS – Université Paris Sud)
sandrine.lacombe@u-psud.fr

Contact

Véronique DEBISSCHOP, (Déléguée Régionale)
Tel.: +33 1 69823272
Fax: +33 1 69823333
E-mail

Subjects

Life Sciences
Record Number: 191496 / Last updated on: 2016-11-21