Folate-targeted iridium complexes amplify photodynamic therapy efficacy through ferroptosis

Abstract

Interest in targeted cancer therapies with fewer side effects has increased in recent years. Photodynamic therapy (PDT) involves the use of photosensitizers (PSs) and light to selectively kill cancer cells, generating highly reactive reactive oxygen species (ROS) that damage cellular components. Here, we synthesized a water-soluble iridium metal complex (Ir-PEG-Fn) with folate-targeting characteristics. PEG endowing the iridium complex with the ability to self-assemble into uniform nanoparticles enhances its permeability and retention effect in tumor cells. The elevation in singlet oxygen (¹O₂) levels led to a reduction in the expression levels of glutathione (GSH) and glutathione peroxidase 4 (GPX4), while concomitantly augmenting the levels of lipid peroxidase (LPO). These physiological responses effectively suppress tumor growth through the manifestation of ferroptosis events. The combination of ferroptosis and PDT has demonstrated excellent anti-cancer efficacy in tumor models in vivo and in vitro.