Heterometallic ruthenium–osmium complexes: dual photodynamic and photothermal therapy for melanoma and drug-resistant lung tumour in vivo

Abstract

A series of hetero-dinuclear Ru–Os complexes have been constructed by combining mononuclear modules derived from homo-dinuclear Ru–Ru complexes with dual PDT/PTT activity and Os–Os complexes with significant PTT activity but no PDT activity. The RuOs6 has improved PDT and PTT effects in comparison to its Ru–Ru and Os–Os parents. The RuOs6 enters cells via caveolar endocytosis, targets the mitochondria but not the nucleus, generates singlet oxygen and releases heat when exposed to IR irradiation, thus inducing cell apoptosis and thermal ablation. In mice, it can entirely eradicate tumors of PDT-resistant melanoma and cisplatin-resistant non-small cell lung tumours. After therapy, only slight metal residue was detected in collected organs of the mice. It also has an extremely low toxicity to normal liver and kidney cells. The PDT driven by an IR low-power laser, and PTT with a moderate temperature increase accomplished by single-molecule RuOs6 are of great significance for the safe treatment of large, deep tumours.