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.