Atomically precise silver clusterzymes protect mice from radiation damages

Abstract Background As 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 hi...

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Autores principales:	Jiao Guo, Haiyu Yang, Ya Liu, Wei Liu, Ruiying Zhao, He Li, Wei Long, Wenqing Xu, Meili Guo, Xiaodong Zhang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Ag14 clusterzymes Atomically precise Renal clearance Radioprotection Biotechnology TP248.13-248.65 Medical technology R855-855.5
Acceso en línea:	https://doaj.org/article/da8b526b72274b93967e9bdf899e0888
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spelling	oai:doaj.org-article:da8b526b72274b93967e9bdf899e08882021-11-21T12:29:41ZAtomically precise silver clusterzymes protect mice from radiation damages10.1186/s12951-021-01054-51477-3155https://doaj.org/article/da8b526b72274b93967e9bdf899e08882021-11-01T00:00:00Zhttps://doi.org/10.1186/s12951-021-01054-5https://doaj.org/toc/1477-3155Abstract Background As 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. Methods The 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. Results Our 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. Conclusion In 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 AbstractJiao GuoHaiyu YangYa LiuWei LiuRuiying ZhaoHe LiWei LongWenqing XuMeili GuoXiaodong ZhangBMCarticleAg14 clusterzymesAtomically preciseRenal clearanceRadioprotectionBiotechnologyTP248.13-248.65Medical technologyR855-855.5ENJournal of Nanobiotechnology, Vol 19, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Ag14 clusterzymes Atomically precise Renal clearance Radioprotection Biotechnology TP248.13-248.65 Medical technology R855-855.5
spellingShingle	Ag14 clusterzymes Atomically precise Renal clearance Radioprotection Biotechnology TP248.13-248.65 Medical technology R855-855.5 Jiao Guo Haiyu Yang Ya Liu Wei Liu Ruiying Zhao He Li Wei Long Wenqing Xu Meili Guo Xiaodong Zhang Atomically precise silver clusterzymes protect mice from radiation damages
description	Abstract Background As 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. Methods The 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. Results Our 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. Conclusion In 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
format	article
author	Jiao Guo Haiyu Yang Ya Liu Wei Liu Ruiying Zhao He Li Wei Long Wenqing Xu Meili Guo Xiaodong Zhang
author_facet	Jiao Guo Haiyu Yang Ya Liu Wei Liu Ruiying Zhao He Li Wei Long Wenqing Xu Meili Guo Xiaodong Zhang
author_sort	Jiao Guo
title	Atomically precise silver clusterzymes protect mice from radiation damages
title_short	Atomically precise silver clusterzymes protect mice from radiation damages
title_full	Atomically precise silver clusterzymes protect mice from radiation damages
title_fullStr	Atomically precise silver clusterzymes protect mice from radiation damages
title_full_unstemmed	Atomically precise silver clusterzymes protect mice from radiation damages
title_sort	atomically precise silver clusterzymes protect mice from radiation damages
publisher	BMC
publishDate	2021
url	https://doaj.org/article/da8b526b72274b93967e9bdf899e0888
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Atomically precise silver clusterzymes protect mice from radiation damages

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