Death receptors (DR4 and DR5) offer attractive targets for cancer treatment because cancer cell death can be induced by apoptotic signal upon binding of death ligands such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) with death receptors. Cyclometalated iridium(III) complexes such as fac-Ir(tpy)₃ (tpy = 2-(4-tolyl)pyridine) possess a C₃-symmetric structure like TRAIL and exhibit excellent luminescence properties. Therefore, cyclometalated Ir complexes functionalized with DR-binding peptide motifs would be potent TRAIL mimics to detect cancer cells and induce their cell death. In this study, we report on the design and synthesis of C₃-symmetric and luminescent Ir complex-peptide hybrids (IPHs), which possess cyclic peptide that had been reported to bind DR5. The results of 27 MHz quartz-crystal microbalance (QCM) measurements of DR5 with IPHs and costaining experiments of IPHs and anti-DR5 antibody, suggest that IPHs bind with DR5 and undergo internalization into cytoplasm, possibly via endocytosis. It was also found that IPHs induce slow cell death of these cancer cells in a parallel manner to the DR5 expression level. These results indicate that IPHs may offer a promising tool as artificial luminescent mimics of death ligands to develop a new category of anticancer agents that detect and kill cancer cells.

中文翻译：

---

用于癌症治疗的发光铱复合物肽杂合物（IPH）：用于检测癌细胞和诱导其坏死型细胞死亡的IPH的设计和合成。

死亡受体（DR4和DR5）为癌症治疗提供了有吸引力的靶标，因为在死亡配体（例如肿瘤坏死因子相关凋亡诱导配体（TRAIL））与死亡受体结合后，凋亡信号可以诱导凋亡，从而导致癌细胞死亡。环金属化铱（III）配合物，例如fac -Ir（tpy）₃（tpy = 2-（4-甲苯基）吡啶）具有C ₃对称结构，如TRAIL，并具有出色的发光性能。因此，用DR结合肽基序功能化的环金属化的Ir复合物将是有效的TRAIL模拟物，以检测癌细胞并诱导其细胞死亡。在这项研究中，我们报告了C ₃的设计和合成对称和发光的Ir复杂肽杂化物（IPHs），具有已被报道与DR5结合的环状肽。用IPHs对DR5进行27 MHz石英晶体微天平（QCM）测量的结果以及IPHs和抗DR5抗体的常规实验，表明IPHs与DR5结合并可能通过内吞作用进入细胞质。还发现IPH以与DR5表达水平平行的方式诱导这些癌细胞的缓慢细胞死亡。这些结果表明，IPHs可以作为死亡配体的人工发光模拟物，提供一种有前途的工具，用于开发检测和杀死癌细胞的新型抗癌剂。