Cisplatin, a representative of platinum-based drug, is clinically and widely used in the treatment of various types of malignant cancer. However, its non-selectivity to almost all the cell lines and resistance in long-term use severely limit its scope of use. As biotin-specific uptake systems are overexpressed in many types of tumors but rarely occur in normal tissues, making biotin a promising target for cancer treatment. In the study, we synthesized the Pt(II) complex C2 and determined its biological activities. The existence of biotin enhanced the ability of the complex to target tumors, while the introduction of a naphthalimide compound makes it possible to diagnose tumors and monitor their progress. We have also introduced a known Pt(II) complex DN604, which not only retains the excellent cytotoxicity of platinum drugs, but also inhibits the expression of DNA double-strand breaks (DSBs) repair-related NHEJ protein Ku70 and HR protein Rad51. In summary, we report a novel trifunctional Pt(II) complex that could target tumor cells, monitor tumor progression, and reverse DSBs repair-induced cisplatin-resistance.

顺铂是铂类药物的代表，在临床上广泛用于治疗各种类型的恶性癌症。但是，其对几乎所有细胞系的非选择性和长期使用的抗性严重限制了其使用范围。由于生物素特异性摄取系统在许多类型的肿瘤中都过表达，但在正常组织中很少发生，因此使生物素成为癌症治疗的有希望的靶标。在研究中，我们合成了Pt（II）配合物C2并确定其生物学活性。生物素的存在增强了复合物靶向肿瘤的能力，而引入萘二甲酰亚胺化合物则可以诊断肿瘤并监测其进展。我们还推出了一种已知的Pt（II）复合物DN604，它不仅保留了铂类药物的优异细胞毒性，而且还抑制了DNA双链断裂（DSBs）修复相关的NHEJ蛋白Ku70和HR蛋白Rad51的表达。总而言之，我们报告了一种新型的三功能Pt（II）复合物，该复合物可以靶向肿瘤细胞，监测肿瘤进展和逆转DSB修复诱导的顺铂耐药性。