MasterNanosciences, nanotechnologies

More than 50% of cancer patients undergo radiation therapy 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 surrounding tissues remains a challenge. In order to enhance the therapeutic window of radiotherapy to lead to a better prognosis for difficult-to-treat cancers, it has been proposed to use innovative nanoscintillators that can induce multifaceted radiotherapeutic effects. Nanoscintillators, also known as radioluminescent nanoparticles down‑convert ionizing radiations into visible light, hence act as internal light sources remotely activated by penetrating X-ray. When accumulated in the tumor prior to radiotherapy, nanoscintillators can induce various effects that can synergize. First, when conjugated to photosensitizers, nanoscintillators can induce deep-tissue photodynamic therapy (PDT). This strategy would overcome the shallow penetration of light in tissues, one of the major limitation of PDT. Second, when nanoscintillators emit in the ultraviolet (UV)-range, and more specifically in the UV‑C, direct DNA-damage can be induced. Finally, because nanoscintillators are made of high-Z element, their accumulation in the tumor prior to radiotherapy will create a purely physical effect of radiation dose‑enhancement. This effect is initiated by a higher photoelectric absorption of orthovoltage X-rays by high‑Z elements compared to soft tissues that leads to a higher production of photo- and Auger electrons that enhance the damage to cancer tissues.
While proof-of-concept studies of radiotherapeutic effects of nanoscintillators have already been demonstrated by us and others, our goal is now to provide a comprehensive description of the mechanisms involved during radiotherapy. We leverage a multidisciplinary approach ranging from physics to biology, to preclinical trials. Our approach includes Monte Carlo simulations to guide the design of optimized nanoconjugates, measurements with reactive oxygen species-sensitive fluorescent probes, in vitro experiments performed on 3D models of glioblastoma and pancreatic cultures and preclinical tests. In order to investigate the particular role of the X-ray energy in the overall treatment efficacy, radiotherapy is delivered by monochromatic tunable synchrotron radiation.