Nanoparticles: exquisite tools to improve radiation based therapies

Radiotherapy is used to fight against cancer in about 50 % of all cancer patients. Recently, the addition of nanoparticles (NPs) has been proposed as a new strategy to enhance the effect of radiotherapy. The group observed for the first time that high-Z NPs amplify in particular the effects of fast carbon ions (hadrontherapy). The underlying physical processes have been investigated [1, 2, 3]. However, further understanding of the biological impact, including the localisation of the NPs in the cells and their effect on cell organelles upon irradiation, is still needed. In this presentation, an overview of in vitro studies that demonstrate the efficiency of gold nanoparticles (AuNPs), platinum nanoparticles (PtNPs) and gadolinium-based nanoparticles (GdBN) to amplify medical radiation effects will be presented. As evidenced by different microscopy techniques, the NPs are localized in the cytoplasm and not in the cell nucleus. In particular, GdBN co-localize with lysosomes and AuNPs are found in the proximity of mitochondria. Even though NPs are not present in the nucleus, they may induce the amplification of double strand breaks in the nuclear DNA. We have demonstrated the major role of hydroxyl radicals in the NPs activated amplification of cell killing. The effect of high-Z NPs is attributed to early stage activation by the incident particle track followed by the production of radical clusters close to cytoplasmic organelles such as lysosomes (GdBN) or mitochondria (AuNPs). The group has shown the high potentiality of high-Z nanoparticles to improve the performances of hadrontherapy including thenostic perspectives. However, the biological pathway responsible for the induction of DSBs in nuclear DNA is still under investigation. Based on these results, new generation nanoagents are developed.