Dual Emissive Ir(III) Complexes for Photodynamic Therapy and Bioimaging

Abstract

Photodynamic therapy (PDT) is a cancer treatment still bearing enormous prospects of improvement. Within the toolbox of PDT, developing photosensitizers (PSs) that can specifically reach tumor cells and promote the generation of high concentration of reactive oxygen species (ROS) is a constant research goal. Mitochondria is known as a highly appealing target for PSs, thus being able to assess the biodistribution of the PSs prior to its light activation would be crucial for therapeutic maximization. Bifunctional Ir(III) complexes of the type [Ir(C^N)2(N^N-R)]+, where N^C is either phenylpyridine (ppy) or benzoquinoline (bzq), N^N is 2,2′-dipyridylamine (dpa) and R either anthracene (1 and 3) or acridine (2 and 4), have been developed as novel trackable PSs agents. Activation of the tracking or therapeutic function could be achieved specifically by irradiating the complex with a different light wavelength (405 nm vs. 470 nm respectively). Only complex 4 ([Ir(bzq)2(dpa-acr)]+) clearly showed dual emissive pattern, acridine based emission between 407–450 nm vs. Ir(III) based emission between 521 and 547 nm. The sensitivity of A549 lung cancer cells to 4 evidenced the importance of involving the metal center within the activation process of the PS, reaching values of photosensitivity over 110 times higher than in dark conditions. Moreover, complex 4 promoted apoptotic cell death and possibly the paraptotic pathway, as well as higher ROS generation under irradiation than in dark conditions. Complexes 2–4 accumulated in the mitochondria but species 2 and 4 also localizes in other subcellular organelles.

Tunable Emissive Ir(III) Benzimidazole‐quinoline Hybrids as Promising Theranostic Lead Compounds

“…Interestingly, L1 and L2 did not display cytotoxic activity; however, complexes 1 and 2 presented a high antiproliferative character in dark conditions, yielding IC 50 values of 4.59±0.23 and 3.50±0.17 μM respectively. These results seem to indicate that the bioactivity falls in the Ir(III) fragment, as it has been previously reported by our research group and others for similar cyclometallated Ir(III) complexes [28,41] . Moreover, the introduction of a thiazolyl instead of a pyridyl within the benzimidazole derivative slightly improves the therapeutic potential of the probes.…”

“…These results seem to indicate that the bioactivity falls in the Ir(III) fragment, as it has been previously reported by our research group and others for similar cyclometallated Ir(III) complexes. [28,41] Moreover, the introduction of a thiazolyl instead of a pyridyl within the benzimidazole derivative slightly improves the therapeutic potential of the probes. The low micromolar range of the IC 50 values found for both complexes in A549 cells in dark conditions are comparable to those reported in the literature for similar cyclometallated Ir(III) complexes, [42] corroborating the good prospects of these benzimidazolyl complexes for chemotherapy purposes in lung cancer.…”

Progress of Nanomaterials in Photodynamic Therapy Against Tumor

“…Therefore, the preparation of PSs that target the mitochondria of cancer cells will be the key to maximize the therapeutic potential of PDT. Recently, Redrado et al prepared four novel mitochondria-selective trackable PSs, which are called bifunctional Ir (III) complexes of the type [Ir (CˆN) 2 (NˆN-R)]+, where NˆC is either phenylpyridine (PPY) or benzoquinoline (BZQ), NˆN is 2,20-dipyridylamine (Dpa), and R either anthracene (1 and 3) or acridine (2 and 4) ( Redrado et al, 2021 ). Only complex 4 ([Ir (Bzq) 2 (dpa-acr)]+) clearly shown a dual emission mode.…”

Well‐Defined Tetrazole‐Functional Copolymers as Macromolecular Ligands for Luminescent Ir(III) and Re(I) Metal Species: Synthesis, Photophysical Properties and Application in Bioimaging

“…[31] The use of transition metal complexes as biological probes/imaging agents, including those attached to (co)polymers, is well-known. [32][33][34][35][36] For example, Redrado et al [37] recently described dual-function hybrid systems containing an organic chromophore and Ir(III) species for photodynamic therapy and bioimaging.…”

“…[ 32–36 ] For example, Redrado et al. [ 37 ] recently described dual‐function hybrid systems containing an organic chromophore and Ir(III) species for photodynamic therapy and bioimaging.…”