Water-Soluble Au₂₅ Clusters with Single-Crystal Structure for Mitochondria-Targeting Radioimmunotherapy

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.

Stimuli-Responsive Polymeric Nanomedicine for Enhanced Cancer Immunotherapy

“…The use of Pt nanoassemble-enriched MOFs for the treatment of breast cancer was reported by Zhang et al, heterojunction structured Wo2.9-WSe2-PEG nanoparticles for radiotherapy/PTT/immune checkpoint blockade immunotherapy was demonstrated by Dong et al, a nutritional immunotherapy nanosystem, and Arg-doped PCN-224 composed of Zr and TCPP followed by gelatin coating was designed by Zhang et al for RDT and nitric oxide production stimulators. Hua et al demonstrated Au 25 clusters with a mitochondria-targeting moiety, 3-(triphenylphosphonio)­propane-1-thiolate bromide) or TPP, for radioimmunotherapy . Considering that the effects of radiotherapy-induced ICD are not sufficient for the eradication of distant tumors, the antiprogrammed death ligand 1 encapsulated MnO 2 with surface HA modification as a checkpoint inhibitor delivery platform combined with radiation was designed to overcome this limitation …”

Construction of novel Ag(0)-containing silver nanoclusters by regulating auxiliary phosphine ligands

“…Metal nanoclusters have attracted wide attention because of their atom-precise structures and quantum size effects, which provide an ideal platform for investigating the connection between simple metal complexes and bulk metal nanoparticles. 1–16 In addition, their potential applications in optics, 17–20 catalysis, 21–25 and biomedicine 26–28 encourage us to synthesize novel structured nanoclusters to exploit versatile properties. Among these, nanoclusters with valence electron structures similar to atomic electron structures are considered “superatomic nanoclusters”.…”

An X-ray activatable gold nanorod encapsulated liposome delivery system for mitochondria-targeted photodynamic therapy (PDT)

“…Hua et al reported cationic water-soluble Au 25 clusters for mitochondria-targeting radioimmunotherapy. 20 The introduction of cationic units in ligands enabled the Au 25 (S-TPP) 18 clusters to have gratifying ability to target mitochondria, which significantly enhanced their tumor killing efficacy at low doses of X-ray compared with Au 25 (SG) 18 .…”