Glutathione-Depleting Gold Nanoclusters for Enhanced Cancer Radiotherapy through Synergistic External and Internal Regulations

The therapeutic performance of cancer radiotherapy is often limited by the overexpression of glutathione (GSH) in tumors and low radiation sensitivity of cancerous cells. To address these issues, the facilely prepared histidine-capped gold nanoclusters (Au NCs@His) were adopted as a radiosensitizer with a high sensitization enhancement ratio of ∼1.54. On one hand, Au NCs@His can inherit the local radiation enhancement property of gold-based materials (external regulation); on the other hand, Au NCs@His can decrease the intracellular GSH level, thus preventing the generated reactive oxygen species (ROS) from being consumed by GSH, and arrest the cells at the radiosensitive G2/M phase (internal regulation).