NBTXR3 Radiotherapy-Activated Functionalized Hafnium Oxide Nanoparticles Show Efficient Antitumor Effects Across a Large Panel of Human Cancer Models

PURPOSE: The side effects of radiotherapy induced on healthy tissue limit its use. To overcome this issue and fully exploit the potential of radiotherapy to treat cancers, the first-in-class radioenhancer NBTXR3 (functionalized hafnium oxide nanoparticles) has been designed to amplify the effects of radiotherapy. PATIENTS AND METHODS: Thanks to its physical mode of action, NBTXR3 has the potential to be used to treat any type of solid tumor. Here we demonstrate that NBTXR3 can be used to treat a wide variety of solid cancers. For this, we evaluated different parameters on a large panel of human cancer models, such as nanoparticle endocytosis, in vitro cell death induction, dispersion, and retention of NBTXR3 in the tumor tissue and tumor growth control. RESULTS: Whatever the model considered, we show that NBTXR3 was internalized by cancer cells and persisted within the tumors throughout radiotherapy treatment. NBTXR3 activated by radiotherapy was also more effective in destroying cancer cells and in controlling tumor growth than radiotherapy alone. Beyond the effects of NBTXR3 as single agent, we show that the antitumor efficacy of cisplatin-based chemoradiotherapy treatment was improved when combined with NBTXR3. CONCLUSION: These data support that NBTXR3 could be universally used to treat solid cancers when radiotherapy is indicated, opening promising new therapeutic perspectives of treatment for the benefit of many patients.