Radiosensitization by gold nanoparticles: Will they ever make it to the clinic?

The utilization of gold nanoparticles (AuNPs) as radiosensitizers has shown great promise in pre-clinical research. In the current review, the physical, chemical, and biological pathways via which AuNPs enhance the effects of radiation are presented and discussed. In particular, the impact of AuNPs on the 5 Rs in radiobiology, namely repair, reoxygenation, redistribution, repopulation, and intrinsic radiosensitivity, which determine the extent of radiation enhancement effects are elucidated. Key findings from previous studies are outlined. In addition, crucial parameters including the physicochemical properties of AuNPs, route of administration, dosing schedule of AuNPs and irradiation, as well as type of radiation therapy, are highlighted; the optimal selection and combination of these parameters enable the achievement of a greater therapeutic window for AuNP sensitized radiotherapy. Future directions are put forward as a means to provide guidelines for successful translation of AuNPs to clinical applications as radiosensitizers.