Strategy for Highly Efficient Radioprotection by a Selenium-Containing Polymeric Drug with Low Toxicity and Long Circulation

Abstract

Because of the rapid development and extensive use of nuclear technology, ionizing radiation has become a large threat to human health. Until now, there has been no practicable radioprotector for routine clinical application because of severe side effects, high toxicity, and short elimination half-life. Herein, we develop a highly efficient radioprotection strategy using a selenium-containing polymeric drug with low toxicity and long circulation by removing reactive oxygen species (ROSs). The selenium-containing polymeric drug is prepared by copolymerization of vinyl phenylselenides (VSe) and N-(2-hydroxyethyl) acrylamide (HEA). The in vitro radioprotective efficacy of the polymeric drug is increased by 40% with lower cytotoxicity compared with the small-molecular VSe monomer. Importantly, the radioprotection activity of the polymeric drug shows more remarkable effects both in cell culture and mice model compared to the commercially available drug ebselen and also exhibits a much longer retention time in blood (half-life similar to 10 h). This work may unfold a new area for highly efficient radioprotection by polymeric drugs instead of small-molecular agents.