Facile Nanolization Strategy for Therapeutic Ganoderma Lucidum Spore Oil to Achieve Enhanced Protection against Radiation‐Induced Heart Disease

Abstract Radiotherapy (RT) has been extensively utilized for clinical cancer therapy, however, excessive generation of reactive oxygen species (ROS) is becoming a main cause for radiation‐induced heart disease (RIHD). Ganoderma lucidum spore oil (GLSO) is a popular functional food composite with potent antioxidant activity, but it is compromised by poor solubility and stability for further application. Therefore, a strategy for rational fabrication of GLSO@P188/PEG400 nanosystem (NS) is demonstrated in this study to realize good water solubility and achieve enhanced protection against RIHD. As expected, GLSO@P188/PEG400 NS can attenuate X‐ray‐induced excessive ROS levels thanks to its enhanced free radical scavenging capability, simultaneously protecting on mitochondria from X‐ray irradiation (IR). Moreover, GLSO@P188/PEG400 NS alleviates DNA damage and promotes self‐repair processes against IR, thus recovering G0/G1 proportion back to normal levels. Furthermore, pre‐ and post‐treated GLSO@P188/PEG400 NS demonstrates potential protection on heart from X‐rays in vivo, as evidenced by attenuating cardiac dysfunction and myocardial fibrosis. Meanwhile, the cell antioxidant capacity (including T‐SOD, MDA, and GSH‐x) stays in balance during this process. This study not only provides a promising strategy for facile nanolization of functional food composites with hydrophobic defects but also sheds light on their cardiac protection and action mechanisms against IR‐induced disease.