Atomically precise silver clusterzymes protect mice from radiation damages

Journal of Nanobiotechnology

Xiaodong Zhang¹  Meili Guo²  Ruiying Zhao²  He Li³  Wenqing Xu³  Jiao Guo³  Wei Liu³  Haiyu Yang³  Ya Liu³  Wei Long³ 

[1] Department of Physics and Tianjin Key Laboratory of Low Dimensional Materials Physics and Preparing Technology, School of Sciences, Tianjin University, 300350, Tianjin, China;Department of Physics, School of Science, Tianjin Chengjian University, 300384, Tianjin, China;Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 300192, Tianjin, China;

关键词: Ag clusterzymes;    Atomically precise;    Renal clearance;    Radioprotection;   

DOI  :  10.1186/s12951-021-01054-5

来源: Springer

【 摘 要 】

BackgroundAs we know, radiotherapy plays an irreplaceable role in the clinical management on solid tumors. However, due to the non-specific killing effects of ionizing radiation, normal tissues damages would be almost simultaneous inevitably. Therefore, ideal radioprotective agents with high efficiency and low toxicity are always desirable. In this work, atomically precise Ag14 clusterzymes were developed, and their applications in radioprotection were studied in vitro and in vivo for the first time.MethodsThe ultra-small glutathione supported Ag14 clusterzymes were synthesized by convenient sodium borohydride (NaBH4) reduction of thiolate-Ag (I) complexes and then they were purified by desalting columns. The enzyme-like activity and antioxidant capacity of Ag14 clusterzymes have been tested by various commercial kits, salicylic acid method and electron spin resonance (ESR). Next, they were incubated with L929 cells to evaluate whether they could increase cell viability after γ-ray irradiation. And then Ag14 clusterzymes were intravenously injected into C57 mice before 7 Gy whole-body γ-ray irradiation to evaluate the radioprotection effects in vivo. At last, the in vivo toxicities of Ag14 clusterzymes were evaluated through biodistribution test, hematological details, serum biochemical indexes and histological test in female Balb/c mice with intravenous injection of Ag14 clusterzymes.ResultsOur studies suggested atomically precise Ag14 clusterzymes were potential radioprotectants. Ag14 clusterzymes exhibited unique superoxide dismutase (SOD)-like activity, strong anti-oxidative abilities, especially on •OH scavenging. The Ag14 clusterzymes could effectively improve cell viability through eliminating ROS and prevent DNA damages in cells dealt with γ-ray irradiation. In vivo experiments showed that Ag14 clusterzymes could improve the irradiated mice survival rate by protecting hematological systems and repairing tissue oxidative stress damage generated by γ-ray irradiation. In addition, bio-distribution and toxicological experiments demonstrated that the ultrasmall Ag14 clusterzymes could be excreted quickly from the body by renal clearance and negligible toxicological responses were observed in mice up to 30 days.ConclusionIn summary, atomically precise, ultrasmall and water soluble Ag14 clusterzymes with SOD-like activity were successfully developed and proved to be effective both in vitro and in vivo for radioprotection. Furthermore, with atomically precise molecular structure, Ag14 clusterzymes, on aspect of the catalytic and optical properties, may be improved by structure optimization on atom-scale level for other applications in disease diagnosis and treatment.Graphical Abstract

【 授权许可】

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