Biotin-Targeted Au(I) Radiosensitizer for Cancer Synergistic Therapy by Intervening with Redox Homeostasis and Inducing Ferroptosis

The search for highly selective sensitizers with a novel mechanism for tumor targeting therapy is of considerable interest. In this work, we have developed a series of new biotin-targeted Au(I) complexes. Through systematic biological evaluation and comparison, biotinylated Au(I) complex 3a containing a triphenylphosphine ligand was screened, as it realized both prominent efficient inhibition and selective cytotoxicity to cancer cells, and the effect was better than that of popularly used auranofin. Meanwhile, complex 3a, as a potent radiosensitizer, enhances anticancer effects in vitro and in vivo and has sensitization selectivity. From the action mechanism study, we provide evidence that complex 3a could intervene in redox homeostasis through targeted binding and strong suppression of thioredoxin reductase (TrxR) and induce the ferroptosis death process, enabling it to sensitize tumor cells to radiotherapy. Thus, complex 3a has enormous potential as an efficient and specific radiosensitizing agent in cancer therapy.

Automated summary

We have developed a novel biotin-targeted gold(I) complex with high selectivity and a unique mechanism for tumor targeting therapy. This complex shows remarkable inhibition of cancer cells and is more effective than the commonly used auranofin. It also acts as a potent radiosensitizer with selective anticancer effects. The complex intervenes in redox homeostasis and induces ferroptosis death, sensitizing tumor cells to radiotherapy.