Nanoparticles in proton and heavy ion therapy

Introduction :Radiotherapy, one of the main treatments in cancer, can be improved by the use of heavy atoms, as radiation enhancers. Many investigations are conducted in this area. The challenge is to increase the radiation... [ view full abstract ]

Introduction :Radiotherapy, one of the main treatments in cancer, can be improved by the use of heavy atoms, as radiation enhancers. Many investigations are conducted in this area. The challenge is to increase the radiation damage on tumor whilst preserving healthy tissue by improving targeting. Recent developments in nanotechnology brought new perspectives by using nanoparticles (NP), which can be specifically functionalized.
Methods :We studied, using plasmid probes, the complex molecular damage radio-enhancement induced by NP. The effect at cellular scale was investigated by clonogenic assay. The internalisation and localisation of NP in cells was performed by complementary methods of microscopy (confocal, electronic...).
Results :We have shown, using plasmid probes, that platinum nanoparticles (PtNP) strongly enhance complex molecular damage induced as well by carbon ions [1], as by protons [2] or gamma rays [3]. This effect is not due to the nature of the incoming radiation but explained by the auto-amplification of electron cascades into the nanoparticles. Similar results were found with gadolinium based nanoparticles (GBN) which give the possibility to associate RMN imaging to radiotherapy. Furthermore, a decrease of mammalian cell survival was also observed when GBN or PtNP are associated to ions radiation [4].
Discussion :These results allow us to measure how the use of heavy nanoparticles could improve treatments by enhancing efficiency and targeting of radiations into the tumor. Further assays are in progress to understand the biological mechanisms underlying these effects [5]. New nanoparticles are considered to find the best candidate.

[1] Porcel et al. Platinum nanoparticles: a promising material for future cancer therapy? Nanotechnology 21, 85103 (2010).
[2] Schlathölter et al. Improving proton therapy by metal-containing nanoparticles: nanoscale insights. International Journal of Nanomedicine 11, 1549-1556 (2016).
[3] Porcel et al. Nano-Sensitization under gamma rays and fast ion radiation. J. Phys.: Conf. Ser. 373 (2012).
[4] Porcel et al. The use of theranostic gadolinium-based nanoprobes to improve radiotherapy performances. Nanomedicine 10 (2014).
[5] Stefancikova et al. Effect of gadolinium‑based nanoparticles on nuclear DNA damage and repair in glioblastoma tumor cells. Journal of Nanobiotechnology 14 :63 (2016).