We report the rational design and photodynamic anticancer mechanism studies of iridium(iii) complexes with pH-responsive singlet oxygen (¹O₂) production and lysosome-specific imaging properties.

The combination of chemotherapeutic and photodynamic activities in an iridium-based molecular compound is less reported. Herein, two iridium complexes (IrC1 and IrC2) with β-carboline alkaloid ligands were designed and synthesized. Both complexes exhibited high anticancer activities with IC₅₀ values of around 1 μM in the dark against several cell lines tested. Notably, the cytotoxicity of these two complexes against lung cancer (A549) cells increased significantly under light (425 nm) irradiation, with phototoxicity index (PI) values of 120 and 93, respectively. They were specifically enriched in the mitochondria. Cell-based assays demonstrated that IrC1 induced an increase in intracellular reactive oxygen species (ROS) levels, reduction in ATP production, mitochondrial DNA damage, an increase in lipid peroxidation levels, and proteasomal activity inhibition. Under light conditions (in some cases a two-photon laser was also applied), these effects were greatly enhanced. Overall, we have demonstrated that these iridium complexes have dual activities of chemotherapy and photodynamic therapy, which may help to design new metal-based anticancer agents for combined chemo-photodynamic therapy.

Metal N-heterocyclic carbene (NHC) complexes represent a promising class of anticancer therapeutic agents. In this work, four cyclometalated iridium(III) complexes (Ir1–Ir4) containing N-heterocyclic carbene ligands have been explored as mitochondrial anticancer and photodynamic agents. These complexes are more cytotoxic than cisplatin against the cancer cells screened, can quickly penetrate into A549 cells and are mainly localized in the mitochondria. Mechanism studies show that these complexes exert their anticancer efficacy by increasing the intracellular ROS level, reducing the mitochondrial membrane potential (MMP) and inducing apoptosis. Additionally, Ir1–Ir4 exhibited two orders of magnitude higher cytotoxicity upon irradiation at 450 nm LED light. Our work provides a strategy for the design of highly effective anticancer photodynamic therapeutic agent based phosphorescent iridium complexes.

Metal/N-heterocyclic carbene (NHC) complexes hold great opportunities for the development of novel antitumor metallodrugs. Herein, four Ag(i) and Au(i

Supramolecular self-assembled nanoparticles were constructed to overcome cisplatin resistance using a platinum(iv) prodrug and porphyrin as the host and guest molecules, respectively.