A Multi-action and Multi-target Ru(II) -Pt(IV) Conjugate Combining Cancer-Activated Chemotherapy and Photodynamic Therapy to Overcome Drug Resistant Cancers.

PtII complexes are commonly used to treat cancer. To reduce their side effects and improve their pharmacological properties, PtIV complexes are being developed as prodrug candidates that are activated by reduction in cancer cells. Concomitantly, RuII polypyridine complexes have gained much attention as photosensitizers for use in photodynamic therapy due to their attractive characteristics. In this article, a novel PtIV -RuII conjugate, which combines cancer activated chemotherapy with PDT, is presented. Upon entering the cancer cell, the PtIV centre is reduced to PtII and the axial ligands including the RuII complex and phenylbutyrate are released. As each component has its individual targets, the conjugate exerts a multi-target and multi-action effect with (photo-)cytotoxicity values upon irradiation up to 595 nm in the low nanomolar range in various (drug resistant) 2D monolayer cancer cells and 3D multicellular tumour spheroids.

Karges J ，Yempala T ，Tharaud M ，Gibson D ，Gasser G ... -  《-》

Biotin-Pt(IV)-Ru(II)-Boron-Dipyrromethene Prodrug as "Platin Bullet" for Targeted Chemo- and Photodynamic Therapy.

Bera A ，Nepalia A ，Upadhyay A ，Saini DK ，Chakravarty AR ... -  《-》

A Cancer Cell-Selective and Low-Toxic Bifunctional Heterodinuclear Pt(IV)-Ru(II) Anticancer Prodrug.

Ma L ，Lin X ，Li C ，Xu Z ，Chan CY ，Tse MK ，Shi P ，Zhu G ... -  《-》

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 ... -  《-》

Design of a Tris-Heteroleptic Ru(II) Complex with Red-Light Excitation and Remarkably Improved Photobiological Activity.

Li S ，Zhao J ，Wang X ，Xu G ，Gou S ，Zhao Q ... -  《-》