Abstract
Radiotherapy remains a cornerstone in cancer treatment, used in over 50% of cases. It employs ionizing radiation, primarily X-rays, to target and destroy tumors through direct DNA damage and indirect effects via reactive oxygen species. Despite technological advancements improving precision of the delivered dose to the tumor, radiotherapy faces critical challenges, particularly damage to healthy tissues, which limits the maximum safe dose. Recent years have seen significant improvements in radiation delivery, including advanced imaging for real-time tumor tracking and combinations with immunotherapy. However, the need for innovative strategies to enhance radiotherapy's therapeutic index remains essential. The radioenhancer NBTXR3 could represent a solution in addressing these limitations. This nanotechnology has been designed to amplify radiotherapy's effects within tumors without increasing toxicity in non-injected adjacent healthy tissues. Beyond better cancer cell destruction and tumor control, radiotherapy-activated NBTXR3 nanoparticles can also stimulate systemic antitumor immune responses in preclinical models. This review aims to provide a comprehensive analysis of preclinical research on NBTXR3, focusing on its mechanism of action and role in initiating and enhancing antitumor immune responses.