Henan Key Laboratory of Crystalline Molecular Functional Materials, Green Catalysis Center, College of Chemistry, Henan International Joint Laboratory of Tumor Theranostic Cluster Materials, Zhengzhou University, Zhengzhou 450001, China.
School of Basic Medical Sciences, College of Medicine, Zhengzhou University, Zhengzhou 450001, China.
ACS Nano. 2023 Apr 25;17(8):7837-7846. doi: 10.1021/acsnano.3c01068. Epub 2023 Apr 6.
Atomically precise gold clusters play an important role in the development of high--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 Au(S-TPP) 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 Au(SG) clusters (SG = glutathione), Au(S-TPP) 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.
原子精确的金纳米簇在高元素基放射增敏剂的发展中起着重要作用，因为它们具有有趣的结构多样性和在关联结构与性能方面的优势。然而，具有水溶性和单晶结构的金纳米簇的合成仍然是一个挑战。在这项研究中，通过配体设计获得了具有线粒体靶向能力和水溶性的原子精确的 Au(S-TPP)纳米簇（TPP-SNa = 溴化 3-(三苯基膦)丙酸钠），以增强放射免疫治疗。与 Au(SG)纳米簇（SG = 谷胱甘肽）相比，由于具有线粒体靶向能力、更高的 ROS 产生能力以及对硫氧还蛋白还原酶（TrxR）的明显抑制作用，Au(S-TPP)表现出更高的放射增敏效率。此外，增强的放射治疗触发的远隔效应与检查点阻断相结合，显示出对远处肿瘤的有效生长抑制。这项工作揭示了金属纳米簇通过配体调控细胞器靶向的能力，通过这种能力可以实现促进其在精准治疗中的应用的可行策略。
