Ultrasmall glutathione-protected gold nanoclusters as next generation radiotherapy sensitizers with high tumor uptake and high renal clearance

    Radiotherapy is often the most straightforward first line cancer treatment for solid tumors. While it is highly effective against tumors, there is also collateral damage to healthy proximal tissues especially with high doses. The use of radiosensitizers is an effective way to boost the killing efficacy of radiotherapy against the tumor while drastically limiting the received dose and reducing the possible damage to normal tissues. Here,we report the design and application of a good radiosensitizer by using ultrasmall Au29–43(SG)27–37 nanoclusters (,2 nm) with a naturally-occurring peptide (e.g., glutathione or GSH) as the protecting shell.

    The GSH-coated Au29–43(SG)27–37 nanoclusters can escape the RES absorption, leading to a good tumor uptake (,8.1% ID/g at 24 h post injection). As a result, the as-designed Au nanoclusters led to a strong enhancement for radiotherapy, as well as a negligible damage to normal tissues. After the treatment, the ultrasmall Au29–43(SG)27–37 nanoclusters can be efficiently cleared by the kidney, thereby avoiding potential long-term side-effects caused by the accumulation of gold atoms in the body. Our data suggest that the ultrasmall peptide-protected Au nanoclusters are a promising radiosensitizer for cancer radiotherapy.

    Ultra-small gold clusters have been shown to have great potential in biomedical applications; however, it is crucial that the targeting clusters can be rapidly excreted from the body. We prepared epidermal growth factor receptor (EGFR) antibody–gold cluster conjugates with tumour-specific targeting, which also enhanced the effects of therapeutic radiation and had good renal clearance properties. We systematically investigated the effects of these clusters on targeted radiation treatment, renal clearance and toxicity over a period of 25 days in mice. The as-prepared EGFR antibody–gold cluster conjugates showed higher in vitro uptakes than gold clusters alone in treated HeLa cells and resulted in enhanced cancer radiation treatment compared with non-specific gold clusters. The in vivo treatment and improved tumour uptake showed that the EGFR antibody–gold cluster conjugates could result in higher tumour uptake and higher tumour ablation. The EGFR antibody–gold cluster conjugates showed 43% excretion in urine after 24 h, only slightly lower than that of the pure gold clusters (52%). Haematological and biochemical studies showed that the conjugates did not cause liver or kidney toxicity 30 days after injection. Therefore, the use of targeting EGFR antibody– gold cluster conjugates with low toxicities and good renal excretion can enhance radiation treatment and is promising in a number of medical applications.

论文：Ultrasmall glutathione-protected gold nanoclusters as next generation radiotherapy sensitizers with high tumor uptake and high renal clearance

作者：XiaoDong Zhang#, Zhentao Luo, Jie Chen, Shasha Song, Xun Yuan, Xiu Shen, Hao Wang, Yuanming Sun, Kai Gao, Lianfeng Zhang, Saijun Fan, David Tai Leong, Meili Guo*, and Jianping Xie* 

发表时间：2015-12-9
期刊：Scientific Reports2015, 5: doi: 10.1038/srep08669  SCI:5.578