Xie Jiani, Wang Chengyan, Wang Ning, Zhu Shuang, Mei Linqiang, Zhang Xiao, Yong Yuan, Li Lele, Chen Chunying, Huang Changshui, Gu Zhanjun, Li Yuliang, Zhao Yuliang
College of Pharmacy and Biological Engineering, Chengdu University, Chengdu, 610106, China; CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China.
CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China; Center of Materials Science and Optoelectronics Engineering, College of Materials Science and Optoelectronic Technology, University of Chinese Academy of Sciences, Beijing, 100049, China.
Biomaterials. 2020 Jun;244:119940. doi: 10.1016/j.biomaterials.2020.119940. Epub 2020 Mar 6.
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.
当使用放射疗法治疗邻近胃肠道组织的腹部肿瘤时，X射线辐射对胃肠道产生的毒性成为一个重大的临床问题，这不仅常常使这些肿瘤无法接受确定的治疗剂量，还会引发一系列胃肠道疾病，如厌食、腹痛、腹泻和便血。因此，这严重降低了患者的治疗效果和生活质量。所以，开发胃肠道辐射防护剂至关重要。然而，临床上可用的商业胃肠道辐射防护剂仍然很少。鉴于此，我们制备了牛血清白蛋白（BSA）修饰的石墨炔（GDY）纳米颗粒（GDY-BSA NPs），并首次研究了其胃肠道辐射防护能力。GDY纳米材料的独特优势，包括高自由基清除能力、在胃酸条件下良好的化学稳定性、在胃肠道中相对较长的停留时间以及口服时良好的生物安全性，为其用作胃肠道辐射防护剂提供了有利的前提条件。体外实验结果表明，GDY-BSA NPs能有效减少DNA损伤并提高受辐照胃肠道细胞的活力。体内结果显示，GDY-BSA NPs显著降低了辐射诱导的小鼠腹泻、体重减轻和胃肠道组织病理损伤。此外，我们还深入研究了GDY-BSA NPs的胃肠道辐射防护机制，结果表明GDY-BSA NPs有效抑制了活性氧（ROS）诱导的凋亡信号通路，从而减少了胃肠道细胞凋亡。我们的工作首次采用BSA-GDY NPs减轻辐射诱导的胃肠道损伤，这不仅促进了新型胃肠道辐射防护剂的探索，也为纳米药物治疗胃肠道疾病提供了良好的指导。
