Chemical Mechanisms of Nanoparticle Radiosensitization and Radioprotection: A Review of Structure-Function Relationships Influencing Reactive Oxygen Species

Metal nanoparticles are of increasing interest with respect to radiosensitization. The physical mechanisms of dose enhancement from X-rays interacting with nanoparticles has been well described theoretically, however have been insufficient in adequately explaining radiobiological response. Further confounding experimental observations is examples of radioprotection. Consequently, other mechanisms have gained increasing attention, especially via enhanced production of reactive oxygen species (ROS) leading to chemical-based mechanisms. Despite the large number of variables differing between published studies, a consensus identifies ROS-related mechanisms as being of significant importance. Understanding the structure-function relationship in enhancing ROS generation will guide optimization of metal nanoparticle radiosensitisers with respect to maximizing oxidative damage to cancer cells. This review highlights the physico-chemical mechanisms involved in enhancing ROS, commonly used assays and experimental considerations, variables involved in enhancing ROS generation and damage to cells and identifies current gaps in the literature that deserve attention. ROS generation and the radiobiological effects are shown to be highly complex with respect to nanoparticle physico-chemical properties and their fate within cells. There are a number of potential biological targets impacted by enhancing, or scavenging, ROS which add significant complexity to directly linking specific nanoparticle properties to a macroscale radiobiological result.