Photodynamic therapy (PDT) is intrinsically restricted by the low penetration depth of light in tissue and is therefore mostly used to treat superficial or optical-fiber accessible lesions. An elegant non-invasive approach to overcome this limitation is to conjugate the photosensitizers to radioluminescent nanomaterials, also called nanoscintillators, and to activate these with radiation therapy. Upon X-ray irradiation, nanoscintillators are “switched on” and emit light that can subsequently excite the photosensitizer and induce PDT. As X-rays penetrate deeply in tissues, radioluminescence can activate PDT non-invasively at depth and without being restricted by large tumor volumes and optical shielding by blood vessels. The feasibility of exciting photosensitizers using nanoscintillators has been demonstrated, but the effects of this complex concept may stem from several therapeutic contributions that remain under-investigated. In this presentation, we report on the investigation of two confirmed contributions: 1) a potential synergy between low dose PDT and radiation therapy, and 2) a radiation dose enhancement effect stemming from increased radiation absorption by nanoscintillators composed of high-Z elements. The combination between low dose PDT and radiation therapy was assessed on heterocellular spheroid models of pancreatic cancer. The ability of nanoscintillators to induce radiation dose enhancement was experimentally assessed on 3D models of glioma, using synchrotron radiation to deliver radiation therapy. For this research, synchrotron radiation offers the unique opportunity to monochromatize the beam and tune its energy to an optimal value.