Targeting cGAS-STING: modulating the immune landscape of hepatic diseases.

Liver diseases, including viral hepatitis, alcoholic liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), and hepatocellular carcinoma (HCC), represent a significant threat to global health due to their high mortality rates. The cGAS-STING pathway, a critical part of the innate immune system, plays a crucial role in detecting cytoplasmic DNA and initiating immune responses, including autoimmune inflammation and antitumor immunity. Genomic instability during cancer progression can trigger this pathway by releasing DNA into the cytoplasm.

Inhibition of autophagic flux by cyclometalated iridium(iii) complexes through anion transportation.

Synthetic anion transporters that can interfere with the intracellular pH homeostasis are gaining increasing attention for tumor therapy, however, the biological mechanism of anion transporters remains to be explored. In this work, two phosphorescent cyclometalated Ir(iii) complexes containing 2-phenylpyridine (ppy) as the cyclometalated ligand, and 2,2'-biimidazole (Hbiim, ) or 2-(1-imidazol-2-yl)pyridine (Hpyim, ) as the ancillary ligands have been synthesized and characterized. Due to the protonation and deprotonation process of the N-H groups on Hbiim and Hpyim, and display pH-dependent phosphorescence and can specifically image lysosomes.

Anticancer Cyclometalated Iridium(III) Complexes with Planar Ligands: Mitochondrial DNA Damage and Metabolism Disturbance.

Emerging studies have shown that mitochondrial DNA (mtDNA) is a potential target for cancer therapy. Herein, six cyclometalated Ir(III) complexes Ir1-Ir6 containing a series of extended planar diimine ligands have been designed and assessed for their efficacy as anticancer agents. Ir1-Ir6 show much higher cytotoxicity than cisplatin and they can effectively localize to mitochondria.

Dual Functions of Cyclometalated Iridium(III) Complexes: Anti-Metastasis and Lysosome-Damaged Photodynamic Therapy.

Four phosphorescent cyclometalated iridium(III) complexes containing benzimidazole moiety have been designed and synthesized. These Ir(III) complexes can effectively inhibit several cancerous processes, including cell migration, invasion, colony formation, and angiogenesis. Interestingly, they show a much higher singlet oxygen quantum yield in an acidic solution than in a neutral solution.

Light-Up Mitophagy in Live Cells with Dual-Functional Theranostic Phosphorescent Iridium(III) Complexes.

Phosphorescent Ir(III) complexes are expected to be new multifunctional theranostic platforms that enable the integration of imaging capabilities and anticancer properties. Mitophagy is an important selective autophagic process that degrades dysfunctional mitochondria. Until now, the regulation of mitophagy is still poorly understood.

Targeting cancer cell metabolism with mitochondria-immobilized phosphorescent cyclometalated iridium(iii) complexes.

Cancer cell metabolism is reprogrammed to sustain the high metabolic demands of cell proliferation. Recently, emerging studies have shown that mitochondrial metabolism is a potential target for cancer therapy. Herein, four mitochondria-targeted phosphorescent cyclometalated iridium(iii) complexes have been designed and synthesized.

Ester-Modified Cyclometalated Iridium(III) Complexes as Mitochondria-Targeting Anticancer Agents.

Organometallic iridium complexes are potent anticancer candidates which act through different mechanisms from cisplatin-based chemotherapy regimens. Here, ten phosphorescent cyclometalated iridium(III) complexes containing 2,2'-bipyridine-4,4'-dicarboxylic acid and its diester derivatives as ligands are designed and synthesized. The modification by ester group, which can be hydrolysed by esterase, facilitates the adjustment of drug-like properties.

Tumor-targeted supramolecular nanoparticles self-assembled from a ruthenium-β-cyclodextrin complex and an adamantane-functionalized peptide.

We report here a supramolecular strategy to assemble a cyclodextrin-functionalized anticancer Ru(ii) complex with an adamantane-appended tumor-targeting peptide into discrete and stable phosphorescent nanostructures that can induce cell death in integrin αβ-rich tumor cells with high selectivity. This strategy presents new opportunities for the construction of tumor-targeting metallo-anticancer therapeutics.

Mono- and Dinuclear Phosphorescent Rhenium(I) Complexes: Impact of Subcellular Localization on Anticancer Mechanisms.

Elucidation of relationship among chemical structure, cellular uptake, localization, and biological activity of anticancer metal complexes is important for the understanding of their mechanisms of action. Organometallic rhenium(I) tricarbonyl compounds have emerged as potential multifunctional anticancer drug candidates that can integrate therapeutic and imaging capabilities in a single molecule. Herein, two mononuclear phosphorescent rhenium(I) complexes (Re1 and Re2), along with their corresponding dinuclear complexes (Re3 and Re4), were designed and synthesized as potent anticancer agents.

Cyclometalated iridium(iii) complexes as lysosome-targeted photodynamic anticancer and real-time tracking agents.

Stimuli-activatable photosensitizers (PSs) are highly desirable for photodynamic therapy (PDT) to selectively demolish tumor cells. On the other hand, lysosomes are emerging as attractive anticancer targets. Herein, four cyclometalated iridium(iii)-β-carboline complexes with pH-responsive singlet oxygen (O) production and lysosome-specific imaging properties have been designed and synthesized.

Cyclometalated Ir(III) complexes as targeted theranostic anticancer therapeutics: combining HDAC inhibition with photodynamic therapy.

The successful design and anticancer mechanistic studies of a series of cyclometalated Ir(III) complexes with histone deacetylase inhibitory and photodynamic therapy (PDT) activities are reported.