Atomically precise gold clusters play an important role in the development of high-Z-element-based radiosensitizers, due to their intriguing structural diversity and advantages in correlating structures and properties. However, the synthesis… Click to show full abstract
Atomically precise gold clusters play an important role in the development of high-Z-element-based radiosensitizers, due to their intriguing structural diversity and advantages in correlating structures and properties. However, the synthesis of gold clusters with both water-solubility and single-crystal structure remains a challenge. In this study, atomically precise Au25(S-TPP)18 clusters (TPP-SNa = sodium 3-(triphenylphosphonio)propane-1-thiolate bromide) showing both mitochondria-targeting ability and water-solubility were obtained via ligand design for enhanced radioimmunotherapy. Compared with Au25(SG)18 clusters (SG = glutathione), Au25(S-TPP)18 exhibited higher radiosensitization efficiency due to its mitochondria-targeting ability, higher ROS production capacity, and obvious inhibition upon thioredoxin reductase (TrxR). In addition, the enhanced radiotherapy-triggered abscopal effect in combination with checkpoint blockade displayed effective growth inhibition of distant tumors. This work reveals the ligand-regulated organelle targeting ability of metal clusters by which feasible strategies to promote their application in precise theranostics could be realized.
               
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