Nanoscintillators-Induced Deep-Tissue Photodynamic Therapy Upon X-Rays Irradiation

International audiencePhotodynamic therapy (PDT) is a cancer therapy that demonstrates promising results for the treatment of several cancers including brain, gastrointestinal and ovarian cancers, diseases associated with a dismal prognosis. The PDT efficacy derives from non-toxic molecules (photosensitizers) that generate reactive oxygen species upon light irradiation, inducing cytotoxicity. Although promising, PDT is limited by the shallow penetration of light in tissue and its application remains restricted to small and/or superficial tumors. Recently, it has been proposed to use nanoscintillators to induce deep tissue PDT. Nanoscintillators are down-converting nanoparticles that absorb high energy X-ray photons and emit visible light, that can subsequently excite nearby photosensitizers and induce PDT in deep tissue embedded tumors and across large tumor volumes. Through this mechanism, the RT/PDT combination efficacy is likely to benefit from three contributions: the RT, the PDT and the radiation dose enhancement effect that is observed when high-Z elements are accumulated within a tumor before the RT. Since the introduction of this idea, proofs of concept have been reported, yet many questions remain to be answered.In this communication, we will discuss the effect of low dose PDT combined with RT applied to 3D heterocellular models of pancreatic cancer. We will also present the ongoing project we are developing around X-PDT for brain and ovarian cancers using synchrotron radiation to deliver RT