The current photodynamic therapy (PDT) is majorly hindered by the shallow penetration depth and oxygen dependency, limiting its application to deep-seated solid hypoxic tumors. Thus, it is meaningful to develop efficient X-ray mediated PDT system capable of generating reactive oxygen species (ROS) under both the normoxic and hypoxic conditions. Herein, we report the synthesis and characterization of nanocomposite, YAG:Pr@ZnO@PpIX with an amalgamation of UV-emitting Y2.99Pr0.01Al5O12 (YAG:Pr) nanoscintillator, and zinc oxide (ZnO) and protoporphyrin IX (PpIX) as photosensitizers. YAG:Pr surface was coated with a ZnO layer (similar to 10 nm) by atomic layer deposition, and then PpIX was covalently conjugated via a linker to give YAG:Pr@ZnO@PpIX. The photo- and cathodoluminescence analyses gave the evidences of efficient energy transfer from YAG:Pr to ZnO at similar to 320 nm, and YAG:Pr@ZnO to PpIX at Soret region (350-450 nm). The nanohybrid was able to produce both, Type I and Type II ROS upon direct and indirect photoactivation with UV36snm and UV290mm, respectively. In vitro cytotoxicity of non activated YAG:Pr@ZnO@PpIX in mouse melanoma cells revealed low toxicity, which significantly enhanced upon photoactivation with UV365nm. indicating the photokilling property of the nanohybrid. Overall, our preliminary studies successfully demonstrate the potential of YAG:Pr@ZnO@PpIX to overcome the limited penetration and oxygen-dependency of traditional PDT. (C) 2018 Elsevier Inc. All rights reserved.