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.
Sonodynamic therapy (SDT) has unique advantages in deep tumour ablation due to its deep penetration depth, showing great preclinical and clinical potential. Herein, a platinum(II)-cyanine complex has been designed to...
Osmium(II) complexes usually exhibit an excellent NIR (near-infrared) emission, which conforms to the optical window in a biological system. Here we designed three mitochondria-targeted NIR terpyridine Os(II) complexes photosensitizers, which...
The curative effect
of sorafenib in hepatocellular carcinoma
(HCC) is limited and sorafenib resistance remains a major obstacle
for HCC. To overcome this obstacle, a new photoactive sorafenib-Ru(II)
complex Ru-Sora has been designed. Upon irradiation (λ = 465
nm), Ru-Sora rapidly releases sorafenib and generates reactive oxygen
species, which can oxidize intracellular substances such as GSH. Cellular
experiments show that irradiated Ru-Sora is highly cytotoxic toward
Hep-G2 cells, including sorafenib-resistant Hep-G2-SR cells. Compared
to sorafenib, Ru-Sora has a significant photoactivated chemotherapeutic
effect against Hep-G2-SR cancer cells and 3D Hep-G2 multicellular
tumor spheroids. Furthermore, Ru-Sora inducing apoptosis and ferroptosis
is proved by GSH depletion, GPX4 downregulation, and lipid peroxide
accumulation. Metabolomics results suggest that Ru-Sora exerts photocytotoxicity
by disrupting the purine metabolism, which is expected to inhibit
tumor development. This study provides a promising strategy for enhancing
chemotherapy and combating drug-resistant HCC disease.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.