Liu Guoqiang, Zeng Yuan, Lv Tong, Mao Tengfei, Wei Yen, Jia Shunji, Gou Yanzi, Tao Lei
The Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084, China.
State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China.
Nat Commun. 2020 Dec 4;11(1):6214. doi: 10.1038/s41467-020-20027-0.
Radioprotectors for acute injuries caused by large doses of ionizing radiation are vital to national security, public health and future development of humankind. Here, we develop a strategy to explore safe and efficient radioprotectors by combining Hantzsch's reaction, high-throughput methods and polymer chemistry. A water-soluble polymer with low-cytotoxicity and an excellent anti-radiation capability has been achieved. In in vivo experiments, this polymer is even better than amifostine, which is the only approved radioprotector for clinical applications, in effectively protecting zebrafish embryos from fatally large doses of ionizing radiation (80 Gy X-ray). A mechanistic study also reveals that the radioprotective ability of this polymer originates from its ability to efficiently prevent DNA damage due to high doses of radiation. This is an initial attempt to explore polymer radioprotectors via a multi-component reaction. It allows exploiting functional polymers and provides the underlying insights to guide the design of radioprotective polymers.
用于大剂量电离辐射所致急性损伤的辐射防护剂对国家安全、公众健康以及人类未来发展至关重要。在此,我们开发了一种通过结合汉茨希反应、高通量方法和高分子化学来探索安全高效辐射防护剂的策略。已制备出一种具有低细胞毒性和出色抗辐射能力的水溶性聚合物。在体内实验中,这种聚合物在有效保护斑马鱼胚胎免受致命大剂量电离辐射(80 Gy X射线)方面甚至比氨磷汀(唯一获批用于临床的辐射防护剂)表现更优。机理研究还表明,这种聚合物具有辐射防护能力是源于其能有效防止高剂量辐射导致的DNA损伤。这是通过多组分反应探索聚合物辐射防护剂的初步尝试。它有助于开发功能性聚合物,并为指导辐射防护聚合物的设计提供潜在见解。