Novel [3+2+1] Coordinated Iridium (III) Complexes for Hyperefficient Photodynamic Therapy

Abstract

Efficient photosensitizers are crucial for the success of photodynamic therapy (PDT). Herein, we reported two [3+2+1] coordinated organometallic Iridium (III) complexes (labeled as Ir-C1 and Ir-C4). Ir-C1/C4 can generate both type I and type II reactive oxygen species (ROS). In vitro experiments, Ir-C1/C4 show low biotoxicity and high phototoxicity of half-maximal inhibitory concentration values of 14 nM and 33 nM on rectal cancer cell line HCT116, respectively. Western blot analysis revealed that the Ir-C1/C4 activated ferroptosis, apoptosis, and inhibiting autophagy simultaneously. Proteomics analysis demonstrated that the photosensitizers destroyed the endoplasmic reticulum (ER), blocking the signal transmission and material transfer between the ER and other tissues of the cell, especially the ER to Golgi vesicle-mediated transport. Ir-C1/C4 can achieve better antitumor performance than commercial photosensitizer Chlorin e6 and the ferroptosis activator RSL3 at lower concentrations. The low biotoxicity and high phototoxicity make them ideal candidates for PDT. The findings provide new insights into the design of photosensitizers for metal complexes and have significant implications for the development of PDT and related drugs.