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Herein, we report a neutral iridium complex, [Ir(4-(2-pyridinyl)benzaldehyde)2(acetylacetone)] (Ir-ER), with viscosity-responsive phosphorescent emission intensity and lifetime. Quantitative measurement by two-photon phosphorescent lifetime imaging shows that the viscosity of ER increases significantly in the process of erastin-induced ferroptosis. Our work provides an effective strategy for quantitative measurement of the micro-environmental alternations of subcellular organelles during a specific cell death process. [ABSTRACT FROM AUTHOR]

The microenvironment in tumor is more acidic than that in normal tissues, due to its metabolic shift to glycolysis. Lysosomes and endosomes are important acidic subcellular organelles, and they perform important functions in many processes and cell signaling transduction processes. Recently, phosphorescent metal complexes are emerging as promising antitumor candidates with unique anticancer properties. Due to their environmental sensitive luminescence properties, the acidity-responsive optical properties can be achieved by rational design of the molecular structures. In this review, we mainly summarize the examples of therapeutic phosphorescent metal complexes with acidity-responsive emission as imaging and theranostic applications reported recently. We also try to put forward the challenges and future research directions in this field. The microenvironment in tumor is more acidic than that in normal tissues, due to its metabolic shift to glycolysis. Lysosomes and endosomes are important acidic subcellular organelles, and they perform important functions in many processes and cell signaling transduction processes. Recently, phosphorescent metal complexes are emerging as promising antitumor candidates with unique anticancer properties. Due to their environmental sensitive luminescence properties, the acidity-responsive optical properties can be achieved by rational design of the molecular structures. In this review, we mainly summarize the examples of therapeutic phosphorescent metal complexes with acidity-responsive emission as imaging and theranostic applications reported recently. These complexes show potent anticancer activity either in dark or upon light irradiation, and they can track events associated with lysosomes/endosomes simultaneously. We also try to put forward the challenges and future research directions in this field. [Display omitted] [ABSTRACT FROM AUTHOR]

Ferroptosis is a programmed cell death pathway discovered in recent years, and ferroptosis‐inducing agents have great potential as new antitumor candidates. Here, we report a IrIII complex (Ir1) containing a ferrocene‐modified diphosphine ligand that localizes in lysosomes. Under the acidic environments of lysosomes, Ir1 can effectively catalyze Fenton‐like reaction, produce hydroxyl radicals, induce lipid peroxidation, down‐regulate glutathione peroxidase 4, and result in ferroptosis. RNA sequencing analysis shows that Ir1 can significantly affect pathways related to ferroptosis and cancer immunity. Accordingly, Ir1 can induce immunogenic cells death and suppress tumor growth in vitro, regulate T cell activity and immune microenvironments in vivo. In conclusion, we show the potential of small molecules with ferroptosis‐inducing capabilities for effective cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Ferroptosis is a programmed cell death pathway discovered in recent years, and ferroptosis‐inducing agents have great potential as new antitumor candidates. Here, we report a IrIII complex (Ir1) containing a ferrocene‐modified diphosphine ligand that localizes in lysosomes. Under the acidic environments of lysosomes, Ir1 can effectively catalyze Fenton‐like reaction, produce hydroxyl radicals, induce lipid peroxidation, down‐regulate glutathione peroxidase 4, and result in ferroptosis. RNA sequencing analysis shows that Ir1 can significantly affect pathways related to ferroptosis and cancer immunity. Accordingly, Ir1 can induce immunogenic cells death and suppress tumor growth in vitro, regulate T cell activity and immune microenvironments in vivo. In conclusion, we show the potential of small molecules with ferroptosis‐inducing capabilities for effective cancer immunotherapy. [ABSTRACT FROM AUTHOR]

DNA polymorphism exerts a fascination on a large scientific community. Without crystallographic structural data, clarification of the binding modes between G-quadruplex (G4) and ligand (complex) is a challenging job. In the present work, three porphyrin compounds with different flexible carbon chains (arms) were designed, synthesized and characterized. Their binding, folding and stabilizing abilities to human telomeric G4 DNA structures were comparatively researched. Positive charges at the end of the flexible carbon chains seem to be favorable for the DNA-porphyrin interactions, which were evidenced by the spectral results and further confirmed by the molecular docking calculations. Biological function analysis demonstrated that these porphyrins show no substantial inhibition to Hela, A549 and BEL 7402 cancer cell lines under dark while exhibit broad inhibition under visible light. This significantly enhanced photocytotoxicity relative to the dark control is an essential property of photochemotherapeutic agents. The feature of the flexible arms emerges as critical influencing factors in the cell photocytotoxicity. Moreover, an ROS-mediated mitochondrial dysfunction pathway was suggested for the cell apoptosis induced by these flexible-armed porphyrins. It is found that the porphyrins with positive charges located at the end of the flexible arms represent an exciting opportunity for photochemotherapeutic anti-cancer drug design. [ABSTRACT FROM AUTHOR]