PO-134 Radiosensitizing effect of gold-based nanoparticles for brain tumourtreatment

Abstract

Introduction Metal-based nanoparticles with radiosensitizing aim have promising prospects in the field of radiotherapy. Due to their high X-ray absorption capacity, nanomaterials with high atomic number may indeed improve radiation therapy efficacy in cancer treatment. Clinical trials are ongoing to evaluate the benefit of nanoparticle enhanced radiotherapy. The objective of the present study was to validate the potential of gold nanoparticle enhanced radiotherapy to treat glioblastoma using in silico , in vitro and in vivo approaches. Material and methods Among a panel of 5 gold nanoparticles (AuNPs), an innovative Monte Carlo simulation approach was used to rank the most promising nanoparticles according to their theoretical radiosensitizing effect. In U87-MG glioblastoma cells, the radiosensitizing effect of the selected nano-objects was confirmed by clonogenic assays and cell death processes such as apoptosis, senescence, and mitotic catastrophes were investigated. A brain tumour window model, allowing fluorescence-based imaging was used to evaluate the tumour tissue selectivity of Cy5-labelled nanoparticles. Results and discussions A radiosensitizing effect was determined for 3 among 5 tested AuNPs with a dose modifying factor (DMF) from 0.4 to 0.5 ( i.e. a DMF equal to 0.5 means the treatment is twice as efficient). Our results showed an inverse relationship between the radiosensitizing effects and the AuNPs sizes. Moreover, the nature of the coating influences the triggered cell death process. In case of PVP-coated AuNPs, the cell death was characterised by a radio-induced senescence in relation with a 1.5-fold increase of the reactive oxygen species production. In contrast, smallest PEG-coated AuNPs triggered post-RX mitotic catastrophes, leading to a delayed cell death. For in vivo experiments, a most promising AuNP ( i.e. Au@DTDTPA:Gd) was selected, showing an interesting U87-tumour tissue selectivity. Conclusion After validating the in vitro radiosensitizing effect of small-sized AuNPs, an innovative design was selected for in vivo experiments. Tumour tissue accumulation and selectivity were evidenced for this innovative nanoparticle. We still have to validate the in vivo radiosensitizing effect using an orthotopic U87 model. We will suggest optimised treatment modalities.