Jun-Ying Wang

Radiotherapy is the mainstay for abdomen and pelvis cancers treatment. However, high energy ray would inflict gastrointestinal (GI) system and adversely disrupt the treatment. The anti-oxidative agents provide a potential route for protecting body from radiation-induced injuries. Herein, highly catalytic nanocubes with dislocation structure are developed for treatment of intestinal injury. Structural and catalytic properties show that Mo incorporation can enhance antioxidant activity by dislocation structure in the alloy. In vitro studies showed that PtPdMo improved cell survival by scavenging radiation-induced ROS accumulation. Furthermore, after animals were exposed to lethal dose of radiation, the survival was increased by 50% with the PtPdMo i.p. treatment. Radioprotection mechanism revealed that PtPdMo alleviated the oxidative stress in multi-organs especially the small intestine by inhibiting intestinal epithelium apoptosis, reducing DNA strands breaks and enhancing repairing ability. In addition, PtPdMo protected hematopoietic system by improving the number of bone marrow and peripheral blood cells.

The radiation-induced damage to mitochondrial oxidative respiratory chain could lead to generating of superoxide anions (O²⁻) and secondary reactive oxygen species (ROS), which are the major resources of continuous ROS production after radiation. Scavenging radiation-induced ROS effectively can help mitochondria to maintain their physiological function and relief cells from oxidative stress. Dihydropyridines (DHPs) are biomimetic hydrogen sources that could protect cells against radiation damage. In this study, we designed and synthetized three novel mitochondrial-targeted dihydropyridines (Mito-DHPs) that utilize the mitochondrial membrane potential to enter the organelle and scavenge ROS. MitoTracker confirmed Mito-DHPs accumulation in mitochondria, and the DCFH-DA assay demonstrated effective ROS scavenging activity. In addition, the γ-H2AX and comet assay demonstrated the ability of Mito-DHPs to protect against both radiation and ROS-induced DNA strand breaks. Furthermore, Mito-DHP1 proved to be non-toxic and displayed significant radioprotection activity (p < 0.05) in vitro. Mito-DHPs are therefore promising antioxidants that could penetrate the membrane of mitochondria, scavenge excessive ROS, and protect cells against radiation-induced oxidative damage.