Biosynthesis of fungus-based oral selenium microcarriers for radioprotection and immuno-homeostasis shaping against radiation-induced heart disease.

Abstract

Radiation-induced heart disease (RIHD), characterized by severe oxidative stress and immune dysregulation, is a serious condition affecting cancer patients undergoing thoracic radiation. Unfortunately, clinical interventions for RIHD are lacking. Selenium (Se) is a trace element with excellent antioxidant and immune-modulatory properties. However, its application in heart radioprotection remains challenging. Herein, we developed a novel bioactive <i>Cordyceps militaris</i>-based Se oral delivery system (Se@<i>CM</i>), which demonstrated superior radioprotection effects <i>in vitro</i> against X-ray-induced damage in H9C2 cells through suppressing excessive ROS generation, compared to the radioprotectant Amifostine. Moreover, Se@<i>CM</i> exhibited exceptional cardioprotective effects <i>in vivo</i> against X-ray irradiation, reducing cardiac dysfunction and myocardial fibrosis by balancing the redox equilibrium and modulating the expression of Mn-SOD and MDA. Additionally, Se@<i>CM</i> maintained immuno-homeostasis, as evidenced by the upregulated population of T cells and M2 macrophages through modulation of selenoprotein expression after irradiation. Together, these results highlight the remarkable antioxidant and immunity modulation properties of Se@<i>CM</i> and shed light on its promising application for cardiac protection against IR-induced disease. This research provides valuable insights into developing effective strategies for preventing and managing RIHD.