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高效含硒高分子药物的低毒长循环放射防护策略。

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

机构信息

State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Suzhou 215123, China.

Schepens Eye Research Institute of Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts 02114, United States.

出版信息

ACS Appl Mater Interfaces. 2020 Oct 7;12(40):44534-44540. doi: 10.1021/acsami.0c14000. Epub 2020 Sep 22.

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 -(2-hydroxyethyl) acrylamide (HEA). The 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 ∼ 10 h). This work may unfold a new area for highly efficient radioprotection by polymeric drugs instead of small-molecular agents.

摘要

由于核技术的快速发展和广泛应用,电离辐射已成为人类健康的一大威胁。到目前为止,由于严重的副作用、高毒性和半衰期短,还没有一种可行的辐射防护剂可用于常规临床应用。在此,我们通过清除活性氧(ROS),开发了一种使用含硒聚合物药物的高效辐射防护策略,该药物具有低毒性和长循环特性。含硒聚合物药物是通过乙烯基苯硒醚(VSe)和-(2-羟乙基)丙烯酰胺(HEA)共聚制备的。与小分子 VSe 单体相比,聚合物药物的辐射防护效果提高了 40%,细胞毒性更低。重要的是,与市售药物依布硒啉相比,聚合物药物在细胞培养和小鼠模型中的辐射防护活性表现出更显著的效果,并且在血液中的保留时间也更长(半衰期约 10 小时)。这项工作可能为高效的辐射防护开辟一个新的领域,即用聚合物药物代替小分子药物。

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