To enhance the efficacy of radiation therapy, functionalised core-shell nanoparticles (CS NPs) are used as a radiosensitizer. These NPs can act as a therapeutic agent and carrier for other therapeutic agents. In this study, the first poly-acrylic acid modified silver-coated titanium dioxide NPs were fabricated to evaluate the radiation dose enhancement within the human tissue equivalent polymer gel after investigating the biocompatibility. Macrophage cell line and rats model were used for and study respectively. Two different beam qualities were applied to quantify the radiation dose enhancement with different concentrations of NPs in the polymer gel. The dose enhancement factors (DEFs) indicated that these biocompatible CS NPs are more effective for the radiation dose enhancement at low energy x-rays (80 kV) as compared to the high energy gamma (1.25 MeV Co). These results suggested that functionalised core-shell silver-coated titanium dioxide NPs have great potential as a radiosensitizer in radiation therapy.