Atomically Precise Gold–Levonorgestrel Nanocluster as a Radiosensitizer for Enhanced Cancer Therapy

Abstract

Gold nanoclusters have become promising radiosensitizers due to their ultrasmall size and robust ability to adsorb, scatter, and re-emit radiation. However, most of the previously reported gold nanocluster radiosensitizers do not have a precise atomic structure, causing difficulties in understanding the structure–activity relationship. In this study, a structurally defined gold–levonorgestrel nanocluster consisting of Au8(C21H27O2)8 (Au8NC) with bright luminescence (58.7% quantum yield) and satisfactory biocompatibility was demonstrated as a nanoradiosensitizer. When the Au8NCs were irradiated with X-rays, they produced reactive oxygen species (ROS), resulting in irreversible cell apoptosis. As indicated by in vivo tumor formation experiments, tumorigenicity was significantly suppressed after one radiotherapy treatment with the Au8NCs. In addition, compared with tumors treated with X-rays (4 Gy) alone, tumors treated with the nanosensitizer exhibited an inhibition rate of 74.2%. This study contributes to the development of atomically precise gold nanoclusters as efficient radiosensitizers.

Photo/electrocatalysis and photosensitization using metal nanoclusters for green energy and medical applications

“…The use of X-ray as the light source is most suitable for activating the Au NCs for deep-tissue cancer treatment and biomedical imaging applications, due to its nearly unlimited penetration depth in living tissues and organisms. An interesting review, 99,100 as well as various other recent publications [101][102][103] covering the applications of Au NCs as radiosensitizers are available.…”

Luminescent gold nanoclusters for bioimaging applications

“…An apparent decrease in fluorescence after more than 6 h suggested the efficient clearance of NCs and there is no accumulation leading to cytotoxicity.A proper functionalization of AuNCs also offers opportunities to develop NC-based radiosensitizers for cancer radiotherapy. Jia et al reported atomically precise Au 8 NCs capped with levonorgestrel [Au 8 (C 21 H 27 O 2 ) 8 ] NCs with yellow-green luminescence and a quantum yield of 58.7% as a radiosensitizer for enhanced cancer therapy[93]. The toxicity studies using human oesophageal squamous cancer cells (EC1) showed that when [Au 8 (C 21 H 27 O 2 ) 8 ] was used at a concentration near its IC 10 value, the luminescence of the incubated samples increased from 0 to 8 h. The luminescence, however, disappeared after 24 h indicating endocytosis of NCs.…”

Ultrasmall Au and Ag Nanoclusters for Biomedical Applications: A Review

“…Another merit to employ NCs for cancer treatment is that the ligand of the Au NCs can be engineered and the endowed functions of the Au NCs can be correlated with the surface ligand and the metal core. Recently, Jia et al (2019) reported that an alkynyl-terminated ligand protected Au 8 nanoclusters (Au 8 NCs) and their radio sensitization for tumor targeting. As presented in Figure 5A , the Au 8 (C 2 1 H 2 7 O 2 ) 8 NCs were synthesized through a one-pot method by reacting C 2 1 H 2 8 O 2 (levonorgestrel) with Me 2 SAuCl.…”

“…The radio sensitization effect of the Au 8 NCs were then assessed in vivo by a tumor assay ( Jia et al, 2019 ). The tests with a control group and phosphate-buffered saline (PBS)-treated group were also conducted as comparison.…”