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 O₂^•− 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.

对缺氧和难治性实体瘤的治疗效果有限，阻碍了光动力疗法的实际应用。在此，我们报告了我们对锇-过氧络合物 ( Os2 ) 的研究，该络合物在黑暗中不活跃，但即使在没有氧气的情况下，在光照射下也能释放过氧配体 O ₂ ^•−，并转化为具有细胞毒性的锇复杂（Os1）。在缺氧肿瘤中，无论是否存在辐射，Os1都具有细胞毒性，表现为一种化学治疗药物。同时，光激活的Os2诱导活癌细胞中内源性 1,4-二氢烟酰胺腺嘌呤二核苷酸的光催化氧化，导致铁死亡，这是由谷胱甘肽降解、脂质过氧化物积累和谷胱甘肽过氧化物酶 4 的下调介导的。体内研究证实，Os2可以有效地抑制小鼠实体缺氧肿瘤的生长。提出了一种用金属基药物治疗缺氧肿瘤的有前景的策略。