Towards Novel Photodynamic Anticancer Agents Generating Superoxide Anion Radicals: A Cyclometalated Ir^IIIComplex Conjugated to a Far‐Red Emitting Coumarin

Abstract

Although cyclometalated IrIII complexes have emerged as promising photosensitizers for photodynamic therapy, some key drawbacks still hamper clinical translation, such as operability in the phototherapeutic window and reactive oxygen species (ROS) production efficiency and selectivity. In this work, a cyclometalated IrIII complex conjugated to a far‐red‐emitting coumarin, IrIII–COUPY, is reported with highly favourable properties for cancer phototherapy. IrIII–COUPY was efficiently taken up by HeLa cells and showed no dark cytotoxicity and impressive photocytotoxicity indexes after irradiation with green and blue light, even under hypoxia. Importantly, a clear correlation between cell death and intracellular generation of superoxide anion radicals after visible light irradiation was demonstrated. This strategy opens the door to novel fluorescent photodynamic therapy agents with promising applications in theragnosis.

X-ray tomography of cryopreserved human prostate cancer cells: mitochondrial targeting by an organoiridium photosensitiser

“…Cyclometallated organoiridium(III) octahedral complexes are promising photosensitisers for PDT [12][13][14][15][16][17][18][19][20][21][22]. They possess high photostability and long luminescence lifetimes, together with an ability to permeate cells [23], and generate toxic ROS upon irradiation.…”

Rationally designed ruthenium complexes for 1- and 2-photon photodynamic therapy

“…To overcome these limitations, there is a need for the development of new classes of PSs. Among others, the use of transition metal complexes [6][7][8][9][10][11] and especially, Ru(II) polypyridine complexes are gaining momentum due to their attractive photophysical and chemical properties (i.e., strong luminescence, high singlet oxygen production, high chemical, and photophysical stability) [12][13][14][15][16][17][18][19][20][21][22] , with the compound TLD-1433 having just entered phase II clinical trials for the treatment of non-muscle invasive bladder cancer [23][24][25] . Despite these remarkable properties, the vast majority of Ru(II) polypyridine complexes are excited using either blue or UV-A light.…”

Transformation of COUPY Fluorophores into a Novel Class of Visible‐Light‐Cleavable Photolabile Protecting Groups

“…[11] Conjugatable versionso fC OUPY fluorophores can also be obtainedt hrough N-alkylation of the pyridine heterocycle. [12] On the basis of these precedents, we envisaged the transformation of COUPY fluorophores into novel coumarin-based PPGs for visible-light uncaging. As shown in Scheme 1, we focused on the synthesis of the first COUPY photocage (compound 3)i nw hich benzoic acid was chosen as a model cargo and caged through the formation of an ester bond.…”