Graphdiyne nanoradioprotector with efficient free radical scavenging ability for mitigating radiation-induced gastrointestinal tract damage

Abstract

X-ray irradiation-induced toxicity to gastrointestinal tract become a significant clinical problem when using radiotherapy for treating abdominal tumors neighbored to gastrointestinal tissue, which not only often prevents these tumors from receiving a definitive therapeutic dose but also causes a series of gastrointestinal diseases, such as anorexia, abdominal pain, diarrhea and hematochezia. And thus it seriously reduces the therapeutic outcome and life quality of patients. Therefore, the development of gastrointestinal radioprotectors is essential. However, the commercial gastrointestinal radioprotectors in clinical are still rare. In view of this, we prepared bovine serum albumin (BSA) modified graphdiyne (GDY) nanoparticles (GDY-BSA NPs) and for the first time studied its gastrointestinal radioprotection ability. The unique advantages of GDY nanomaterial, including high free radical scavenging ability, good chemical stability in gastric acid condition, relatively longer residence time in gastrointestinal tract and good biosafety under oral administration, provide the favorable prerequisites for it to be used as the gastrointestinal radioprotector. In vitro experimental results indicated that the GDY-BSA NPs powerfully reduced DNA damage and improved viability of the irradiated gastrointestinal cells. In vivo results showed that the GDY-BSA NPs significantly decrease radiation-induced diarrhea, weight loss, and gastrointestinal tissue pathological damage of mice. Furthermore, we also deeply studied the gastrointestinal radioprotective mechanism of GDY-BSA NPs, which indicated that the GDY-BSA NPs effectively inhibited reactive oxygen species (ROS)-induced apoptosis signal pathway, and thus reduced gastrointestinal cell apoptosis. Our work for the first time employed BSA-GDY NPs to mitigating radiation-induced gastrointestinal tract damage, which not only promotes the exploration of new gastrointestinal tract radioprotectors, but also is the good guidance for the treatment of gastrointestinal diseases by nano-drug.

Keywords: Free radical scavenging; Gastrointestinal tract; Graphdiyne; Nanoradioprotector; Oral activity.