What question did this study set out to answer?

To synthesize and evaluate the anticancer activity of a new iridium(III) complex as a photosensitizer.

April 16, 2026

Synthesis and evaluation of anticancer activity in vitro and in vivo of photoactivated iridium(III) complex

XZXiandong ZengShanghai Jiao Tong University YWYue WangUniversity of Stuttgart STShuanghui TangGuangdong Pharmaceutical University

Key Points

To synthesize and evaluate the anticancer activity of a new iridium(III) complex as a photosensitizer.
Synthesis of [Ir(piq)2(NNIP)]PF6 using NNIP as a ligand.
Assessment of cytotoxicity using the MTT assay on HeLa, B16, and NIH3T3 cells.
Investigation of anticancer mechanisms, including ROS production and mitochondrial dynamics.
Exploration of various types of cell death, including ferroptosis and apoptosis.
In vivo evaluation of tumor growth inhibition.
Ir1 shows no cytotoxicity in the dark (IC50 > 200 μM).
Upon light activation, Ir1 exhibits significant cytotoxicity against HeLa cells (IC50 = 3.1 ± 0.3 μM).
Demonstrated induction of cancer cell death via mitochondrial apoptosis, ROS, and ferroptosis pathways.
In vivo studies reveal a 53.2% reduction in tumor growth.

Abstract

In this article, using NNIP (2-(2-nitronaphthalen-1-yl)-1H-imidazo4,5-f1,10phenanthroline) as a ligand to synthesise and characterise a new iridium(III) complex, Ir(piq)2(NNIP)PF6 (Ir1, where piq = 1-phenylisoquinoline) and to explore its anticancer activity as a photosensitiser against HeLa cancer cells and the corresponding mechanisms of inducing cancer cell death. The cytotoxicity of Ir1 against HeLa, B16 and normal NIH3T3 cells was assessed using the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Unexpectedly, Ir1 initially shows no cytotoxicity against those cells (half maximal inhibitory concentration, IC50 200 μM) in the dark. However, upon white light irradiation, Ir1 significantly increased cytotoxicity, especially on HeLa cancer cells with a low IC50 value of 3.1 ± 0.3 μM. The anticancer mechanism was explored through various techniques, including cellular uptake, mitochondrial co-localisation, ROS production, mitochondrial permeability transition pore opening and the change in the mitochondrial membrane potential. Subsequently, lipid peroxidation was investigated with a C11-BODIPY581/591 probe to affirm the occurrence of ferroptosis. Additionally, metabolic impacts were probed by conducting lactate dehydrogenase release and adenosine 5′-triphosphate (ATP) quantification assays. Apoptosis, pyroptosis and immunogenic cell death were also explored. The light-activated antitumour in vivo revealed that Ir1 can effectively inhibit the tumour growth with an inhibitory rate of 53.2%. These findings demonstrate that Ir1 induces cancer cell demise by a mitochondrial apoptotic pathway mediated by ROS, ferroptosis and pyroptosis.

Ask AI

Helpful

Bookmark

View Full Paper