Luminescent ruthenium(II) polypyridyl complexes acted as radiosensitizer for pancreatic cancer by enhancing radiation-induced DNA damage
Luminescent ruthenium(II) polypyridyl complexes acted as radiosensitizer for pancreatic cancer by enhancing radiation-induced DNA damage
复制标题
发光钌(II)聚吡啶复合物通过增强辐射诱导的DNA损伤作为胰腺癌的放射增敏剂
DOI：
10.7150/thno.34015
复制
发表时间：
2019-01-01
期刊：
影响因子：
12.4
通讯作者：
Zhang, Qi
中科院分区：
文献类型：
--
作者：
Zhou, Yuyang;Xu, Ying;Zhang, Qi
背景：胰腺癌是一种高致死性的恶性肿瘤，在美国和中国分别排在第4和第6位。需要新的药物来改善患者的生存和预后。方法：合成不同DIP配体数目的钌（II）配合物，并将其作为胰腺癌的放射增敏剂。研究了钌（II）配合物对细胞行为和肿瘤生长的影响。用琼脂糖凝胶电泳法测定钌（II）配合物与质粒的DNA结合亲和力。结果如下：发光钌（II）配合物能迅速进入细胞核，与DNA联合收割机结合，增强X射线对DNA的损伤作用。在肿瘤内注射钌（II）络合物后，在人胰腺癌异种移植裸鼠的电离辐射下实现了优异的肿瘤生长抑制。结论：综上所述，我们的研究表明，钌（II）多吡啶配合物可以有效地增强辐射诱导的DNA损伤，这可能是有益的成像引导的癌症放化疗。
Background: Pancreatic cancer is a highly lethal malignancy which ranks 4th most common cause of cancer death in US and 6th in China. Novel drugs are required to improve the survival and prognosis of patients. Methods: Ruthenium(II) complexes with variation number of DIP ligand were synthesized and further adopted as radiosensitizer for pancreatic cancer. The influence of ruthenium(II) complexes on cell behaviors and tumor growth were investigated. The DNA binding affinity of ruthenium(II) complexes and plasmid was measured by using agarose gel electrophoresis. Results: Luminescent ruthenium(II) complex can rapidly enter into cell nuclei and consequently combine with DNA, resulting in the enhanced DNA damage induced by X-ray irradiation. Upon intratumoral injection of ruthenium(II) complex, excellent tumor growth inhibition was accomplished under ionizing radiation of human pancreatic cancer xenograft nude mice. Conclusions: Taken together, our study suggest that the ruthenium(II) polypyridyl complexes can effectively enhance radiation-induced DNA damage, which is likely to benefit the imaging-guided cancer radio-chemotherapy.