Atomically precise silver clusterzymes protect mice from radiation damages

Jiao Guo,Wenqing Xu,Wei Liu,Xiaodong Zhang,Haiyu Yang,Ya Liu,Ruiying Zhao,Meili Guo,He Li,Wei Long

doi:10.1186/s12951-021-01054-5

Abstract

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

Highlights

As we know, radiotherapy plays an irreplaceable role in the clinical management on solid tumors
In summary, atomically precise, ultrasmall and water soluble Ag14 clusterzymes with superoxide dismutase (SOD)-like activity were successfully developed and proved to be effective both in vitro and in vivo for radioprotection
In the process of radiotherapy, ionizing radiation will inevitably cause some damages to normal tissues, which is mainly attributed to exogenous reactive oxygen species (ROS), such as hydroxyl radical (OH) and superoxide anion (O2−), generated by ionization of water molecules through Compton scattering, photoelectric and Auger effects of high energy ionizing radiation [7,8,9,10,11,12]

Summary

Introduction

Radiotherapy plays an irreplaceable role in the clinical management on solid tumors. Nanomaterials with ROS scavenging activity have shown great potential in radiation protection, especially those with rapid renal clearance showing good biocompatibility and low toxicity, such as CeO2, WS2, and MoS2 nanoparticles [23,24,25,26,27,28,29]. Due to their inaccessible molecular structures or heterogeneous size distributions, these nanomaterials face great challenges in improving catalytic activity and bio-selectivity. These nanoclusters were named as metal clusterzymes [32, 33]

Methods

Results

Conclusion