Ruthenium arene complexes in the treatment of 3D models of head and neck squamous cell carcinomas

Current chemotherapy for head and neck squamous cell carcinomas (HNSCCs) are based on cisplatin, which is usually associated to severe side effects. In general, the exploration for metal-based alternatives to cisplatin has resulted in the development of a series of ruthenium complexes that are able to produce a safe therapeutic action against some neoplasms, among which are lung and ovarian cancers. Here, we evaluate the efficacy of well defined, easily available and robust ruthenium(II) η⁶-arene compounds on 3D models of HNSCCs with or without human papillomavirus (HPV) infection and compare their effects to the state-of-the-art RAPTA-C, a promising ruthenium compound with known anti-cancer activity. One of the compounds induces a significant therapeutic action especially on HPV negative carcinoma. Besides viability and repopulation evaluations, we performed quantitative analysis of the internalized Ru compounds to further validate our findings and elucidate the possible mechanisms of action. These results show that Ru arene compounds represent a promising alternative for the treatment of HNSCCs and pave the way for the composition of innovative (co)therapies.