Folate-targeted iridium complexes amplify photodynamic therapy efficacy through ferroptosis

Abstract

Interest in targeted cancer therapies with fewer side effects has increased in recent years. Photodynamic therapy(PDT) uses photosensitizers(PS) and light to selectively kill cancer cells, generating highly reactive reactive oxygen...

A Λ-Ir(iii)-phenylquinazolinone complex enhances ferroptosis by selectively inhibiting metallothionein-1

“…When compared to the first reported Iridium( iii )-based ferroptosis inducer (IrFN), 19 Λ -IrPPQ also displayed higher cytotoxicity toward PANC-1 cells than IrFN (Table S2†). In addition, the photocytotoxicity index of Λ -IrPPQ was higher than most reported ferroptosis-inducing metal agents (Table S2†), 20–26,32–35 confirming the high cancer cell killing efficiency as a potential PDT agent.…”

“…16,17 In particular, for pancreatic ductal adenocarcinoma (PDAC), a ferroptosis-sensitive cell line, deletion of Slc7a11 by ferroptosis inducers resulted in excellent inhibition of PDAC in mice. 18 Recently, the development of metal complexes (Ir( iii ), 19–26 Fe( iii ), 27–31 and Ga( iii ) 32–34 ) by inducing ferroptosis has shown significant advantages in disrupting Fe metabolism, glutathione metabolism and regulating immune responses. In addition, targeting ferroptosis suppressor protein-1 (FSP1, a glutathione-independent ferroptosis suppressor) by an AIE-based Pt( ii ) complex induced ferroptosis with potential to overcome drug resistance.…”

The anticancer application of half-sandwich iridium(iii) ferrocene-thiosemicarbazide Schiff base complexes

“…6 The remarkable anticancer activity and distinct anticancer mechanism of iridium( iii ) (Ir III ) complexes, particularly half-sandwich-shaped Ir III complexes, have made them potential alternatives to cisplatin in recent years. 7–10 Traditional half-sandwich Ir III complexes are usually described as [(η 5 -Cp x )Ir(L^L)Z] 0/+ , where Cp x represents cyclopentadiene or its derivative (phenyl/biphenyl substituents, electron-donating tridentate ligands); L^L represents various chelating ligands, including N^N, C^N, O^N, and O^O, 11 which are currently the most studied; and Z represents the leaving group (Cl − , Br − , I − , pyridine, etc. ).…”

Synthetic ease and exceptional in vivo performance of pyrazole-based cyclometallated iridium complexes

“…1 In addition, they have been reported to function as efficient photosensitisers (PSs) producing reactive oxygen species (ROS), such as the highly cytotoxic singlet oxygen ( 1 O 2 ). 2 This has opened the door to including cyclometallated Ir III complexes within photodynamic therapy, potentially creating multifunctional therapeutic metallodrugs capable of serving as both chemotherapeutics and PSs agents. Additionally, their phosphorescent nature with high quantum yield, large Stokes shifts and long-lived phosphorescence, among other features, makes them also suitable for bioimaging.…”