Ir(III) and Ru(II) Complexes in Photoredox Catalysis and Photodynamic Therapy: A New Paradigm towards Anticancer Applications.

Individually, photoredox catalysis (PC) and photodynamic therapy (PDT) are well-established concepts that have experienced a remarkable resurgence in recent years, leading to significant progress in organic synthesis for PC and clinical approval of anticancer drugs for PDT. But, very recently, new photoredox catalyst systems based on Ir(III) and Ru(II) complexes have garnered significant interest because they can simultaneously be used as PDT agents apart from their demonstrated PC activity. This highlight discusses the unique PC behavior of emerging Ir(III)- and Ru(II)-based systems while also examining their potential PDT activity in cancer treatment.

Raza MK ，Noor A ，Samantaray PK 《-》

Insights into the anticancer photodynamic activity of Ir(III) and Ru(II) polypyridyl complexes bearing β-carboline ligands.

Ir(III) and Ru(II) polypyridyl complexes are promising photosensitizers (PSs) for photodynamic therapy (PDT) due to their outstanding photophysical properties. Herein, one series of cyclometallated Ir(III) complexes and two series of Ru(II) polypyridyl derivatives bearing three different thiazolyl-β-carboline N^N' ligands have been synthesized, aiming to evaluate the impact of the different metal fragments ([Ir(C^N)2]+ or [Ru(N^N)2]2+) and N^N' ligands on the photophysical and biological properties. All the compounds exhibit remarkable photostability under blue-light irradiation and are emissive (605 < λem < 720 nm), with the Ru(II) derivatives displaying higher photoluminescence quantum yields and longer excited state lifetimes. The Ir PSs display pKa values between 5.9 and 7.9, whereas their Ru counterparts are less acidic (pKa > 9.3). The presence of the deprotonated form in the Ir-PSs favours the generation of reactive oxygen species (ROS) since, according to theoretical calculations, it features a low-lying ligand-centered triplet excited state (T1 = 3LC) with a long lifetime. All compounds have demonstrated anticancer activity. Ir(III) complexes 1-3 exhibit the highest cytotoxicity in dark conditions, comparable to cisplatin. Their activity is notably enhanced by blue-light irradiation, resulting in nanomolar IC50 values and phototoxicity indexes (PIs) between 70 and 201 in different cancer cell lines. The Ir(III) PSs are also activated by green (with PI between 16 and 19.2) and red light in the case of complex 3 (PI = 8.5). Their antitumor efficacy is confirmed by clonogenic assays and using spheroid models. The Ir(III) complexes rapidly enter cells, accumulating in mitochondria and lysosomes. Upon photoactivation, they generate ROS, leading to mitochondrial dysfunction and lysosomal damage and ultimately cell apoptosis. Additionally, they inhibit cancer cell migration, a crucial step in metastasis. In contrast, Ru(II) complex 6 exhibits moderate mitochondrial activity. Overall, Ir(III) complexes 1-3 show potential for selective light-controlled cancer treatment, providing an alternative mechanism to chemotherapy and the ability to inhibit lethal cancer cell dissemination.

Sanz-Villafruela J ，Bermejo-Casadesus C ，Zafon E ，Martínez-Alonso M ，Durá G ，Heras A ，Soriano-Díaz I ，Giussani A ，Ortí E ，Tebar F ，Espino G ，Massaguer A ... -  《-》

Bombesin-Targeted Delivery of β-Carboline-Based Ir(III) and Ru(II) Photosensitizers for a Selective Photodynamic Therapy of Prostate Cancer.

Sanz-Villafruela J ，Bermejo-Casadesús C ，Riesco-Llach G ，Iglesias M ，Martínez-Alonso M ，Planas M ，Feliu L ，Espino G ，Massaguer A ... -  《-》

A mitochondria-targeting dinuclear Ir-Ru complex as a synergistic photoactivated chemotherapy and photodynamic therapy agent against cisplatin-resistant tumour cells.

Zhang C ，Guan R ，Liao X ，Ouyang C ，Rees TW ，Liu J ，Chen Y ，Ji L ，Chao H ... -  《-》

A Ru-anthraquinone dyad with triple functions of PACT, photoredox catalysis and PDT upon red light irradiation.

Zhang C ，Guo X ，Da X ，Wang Z ，Wang X ，Zhou Q ... -  《-》