An osmium-peroxo complex for photoactive therapy of hypoxic tumors

The limited therapeutic effect on hypoxic and refractory solid tumors has hindered the practical application of photodynamic therapy. Herein, we report our investigation of an osmium-peroxo complex ( Os2 ), which is inactive in the dark, but can release a peroxo ligand O 2 •− upon light irradiation even in the absence of oxygen, and is transformed into a cytotoxic osmium complex ( Os1 ). Os1 is cytotoxic in the presence or absence of irradiation in hypoxic tumors, behaving as a chemotherapeutic drug. At the same time, the light-activated Os2 induces photocatalytic oxidation of endogenous 1,4-dihydronicotinamide adenine dinucleotide in living cancer cells, leading to ferroptosis, which is mediated by glutathione degradation, lipid peroxide accumulation and down-regulation of glutathione peroxidase 4. In vivo studies have confirmed that the Os2 can effectively inhibit the growth of solid hypoxic tumors in mice. A promising strategy is proposed for the treatment of hypoxic tumors with metal-based drugs. Photodynamic therapy has been a promising technique for the treatment of tumours. In this manuscript, the authors report on the photoactivation of the osmium peroxo complex and its potential use for chemotherapy and photodynamic therapy under blue light irradiation against tumours in their hypoxic environment.