Work

Synergistic photoinduction of ferroptosis and apoptosis by a mitochondria-targeted iridium complex for bladder cancer therapy

Year: 2024

Type: article

Abstract: Bladder cancer (BC) is one of the most common malignant tumors of the urinary system, and has a high recurrence rate and treatment resistance. Recent results indicate that mitochondrial metabolism influences the therapeutic outcomes of BC. Mitochondria-targeted photosensitizer (PS) is a promising anticancer therapeutic approach that may overcome the limitations of conventional BC treatments. Herein, two mitochondria-targeted iridium(III) PSs, Ir-Mito1 and Ir-Mito2, have been designed for BC treatment. Mechanically, Ir-Mito2 induced a decrease in mitochondrial membrane potential via white light activation, further triggering a reduction of the B-cell lymphoma 2 protein (Bcl-2)/Bcl-associated X protein (Bax) ratio and increment of cleaved caspase3. Meanwhile, the reduction of glutathione, deactivation of glutathione peroxidase 4 (GPX4), increase of acyl-CoA synthetase long chain family member 4 (ACSL4), and accumulation of lipid peroxide resulted in synergistically activating of ferroptosis and apoptosis. The results demonstrated that Ir-Mito2 exhibited excellent antitumor efficacy with superior biosafety in vivo. This work on light-activated and mitochondrial-targeted PS provides an innovative therapeutic platform for BC.

Source: Journal of Colloid and Interface Science

DOI: 10.1016/j.jcis.2024.12.073