Nanoscintillators to potentiate brain cancer radiotherapy: from physics to preclinical trials

More than 50% of cancer patients undergo radiation therapy (RT) in the course of their treatment. However, because of a lack of specificity for tumor tissues, delivering therapeutically effective doses of X rays with tolerable toxicity on healthy tissues remains a challenge. Glioblastoma multiforme (GBM), the most common primary brain cancer in adults has a dismal prognosis despite an aggressive standard-of-care. Developing new strategies to improve the therapeutic index of RT is therefore of major importance. The aim of this project is to comprehensively study the multifaceted radiotherapeutic effect of nanoscintillators (NS), and determine how to harness these effects to improve the therapeutic index of RT. By converting high-energy photons such as X-rays into UV/visible photons, NS can augment RT by various effects. These include radiation dose enhancement, radioluminescence-induced photodynamic therapy and DNA damage generated by UV-radioluminescence. This project has three main objectives: 1) To elucidate the physical and photochemical origins of the radiotherapeutic effects of NS using spectroscopic studies to identify the reactive oxygen species and DNA lesions generated upon X-rays; 2) To study the biological impact of the NS on 3D models and in syngeneic rat models of GBM; 3) To develop an in silico program that simulates the efficacy of prospective NS, and studies the impact of their composition, size and morphology. This will tailor future NS to specific malignancies with distinct biological properties. With this innovative methodology and an interdisciplinary approach that ranges from physics to biology, this project will provide ground-breaking fundamental knowledge on the radiotherapeutic effects of NS that may lead to highly valuable and clinically translatable therapies. In the long-term, this strategy may be tailored for pancreatic and metastatic ovarian cancers, for which the multifaceted enhancement of RT efficacy by NS may be of great interest.