Synthesis, characterization and antitumor mechanism investigation of ruthenium(II) polypyridyl complexes with artesunate moiety.

Six artesunate (ART) conjugated ruthenium(II) complexes (Ru(II)-ART conjugates) with the formula [Ru(N^N)2bpy(4-CH3-4'-CH2OART)](PF6)2 (Ru-ART-1-3) and [Ru(N^N)2bpy(4-CH2OART-4'-CH2OART)](PF6)2 (Ru-ART-4-6) (N^N = 2,2'-bipyridine (bpy, in Ru-ART-1 and Ru-ART-4), 1,10-phenanthroline (phen, in Ru-ART-2 and Ru-ART-5) and 4,7-diphenyl-1,10-phenanthroline (DIP, in Ru-ART-3 and Ru-ART-6)), were synthesized and characterized. Among them, Ru-ART-1-3 and Ru-ART-4-6 carry one and two ART moieties, respectively. Ru-ART-3 and Ru-ART-6 exhibit better cytotoxicity among six Ru(II)-ART conjugates. These two complexes can be effectively taken up by human cervical carcinoma (HeLa) cells. In addition, they selectively kill cancer cell lines while mildly affect normal cells. Mechanism studies have shown that HeLa cells treated with Ru-ART-3 and Ru-ART-6 show typical apoptotic characteristics (morphology changes, mitochondrial dysfunction, caspase cascade, etc.). On the other hand, the up regulation of Beclin-1 and conversion of LC3-I to LC3-II note the appearance of autophagy. As a result, Ru-ART-3 and Ru-ART-6 induce autophagy-dependent cell apoptosis via mitochondrial dysfunction and reactive oxygen species (ROS) accumulation. In this work, six artesunate (ART) conjugated ruthenium(II) complexes (Ru(II)-ART conjugates) have been synthesized and characterized. Among them, Ru-ART-3 and Ru-ART-6 exhibit better cytotoxicity. Mechanism studies have shown that HeLa cells treated with Ru-ART-3 and Ru-ART-6 show typical apoptotic characteristics (morphology changes, mitochondrial dysfunction, caspase cascade, etc.). On the other hand, the up regulation of Beclin-1 and conversion of LC3-I to LC3-II note the appearance of autophagy.

Copper-Catalyzed Decarboxylative Cycloaddition of Propiolic Acids, Azides, and Arylboronic Acids: Construction of Fully Substituted 1,2,3-Triazoles.

A copper-catalyzed decarboxylative cycloaddition of propiolic acids, azides, and arylboronic acids is described. The present reaction provides an efficient and convenient method for the synthesis of various fully substituted 1,2,3-triazoles from readily available starting materials. A possible mechanism is proposed.

Valproic Acid-Functionalized Cyclometalated Iridium(III) Complexes as Mitochondria-Targeting Anticancer Agents.

Valproic acid (VPA) is a short-chain, fatty acid type histone deacetylase inhibitor (HDACi), which can cause growth arrest and induce differentiation of transformed cells. Phosphorescent cyclometalated IrIII complexes have emerged as potential anticancer agents. By conjugation of VPA to IrIII complexes through an ester bond, VPA-functionalized cyclometalated iridium(III) complexes 1 a-3 a were designed and synthesized. These complexes display excellent two-photon properties, which are favorable for live-cell imaging. The ester bonds in 1 a-3 a can be hydrolyzed quickly by esterase and display similar inhibition of HDAC activity to VPA. Notably, 1 a-3 a can overcome cisplatin resistance effectively and are about 54.5-89.7 times more cytotoxic than cisplatin against cisplatin-resistant human lung carcinoma (A549R) cells. Mechanistic studies indicate that 1 a-3 a can penetrate into human cervical carcinoma (HeLa) cells quickly and efficiently, accumulate in mitochondria, and induce a series of cell-death-related events mediated by mitochondria. This study gives insights into the design and anticancer mechanisms of multifunctional anticancer agents.

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. The subcellular accumulation of Re1-Re4 was conveniently analyzed by confocal microscopy in situ in live cells by utilizing their intrinsic phosphorescence. We found that increased lipophilicity of the bidentate ligands could enhance their cellular uptake, leading to improved anticancer efficacy. The dinuclear complexes were more potent than the mononuclear counterparts. The molecular anticancer mechanisms of action evoked by Re3 and Re4 were explored in detail. Re3 with a lower lipophilicity localizes to lysosomes and induces caspase-independent apoptosis, whereas Re4 with higher lipophilicity specially accumulates in mitochondria and induces caspase-independent paraptosis in cancer cells. Our study demonstrates that subcellular localization is crucial for the anticancer mechanisms of these phosphorescent rhenium(I) complexes.

Theranostic iridium(III) complexes as one- and two-photon phosphorescent trackers to monitor autophagic lysosomes.

During autophagy, the intracellular components are captured in autophagosomes and delivered to lysosomes for degradation and recycling. Changes in lysosomal trafficking and contents are key events in the regulation of autophagy, which has been implicated in many physiological and pathological processes. In this work, two iridium(III) complexes (LysoIr1 and LysoIr2) are developed as theranostic agents to monitor autophagic lysosomes. These complexes display lysosome-activated phosphorescence and can specifically label lysosomes with high photostability. Simultaneously, they can induce autophagy potently without initiating an apoptosis response. We demonstrate that LysoIr2 can effectively implement two functions, namely autophagy induction and lysosomal tracking, in the visualization of autophagosomal-lysosomal fusion. More importantly, they display strong two-photon excited fluorescence (TPEF), which is favorable for live cell imaging and in vivo applications.

Design, synthesis, and antitumor mechanism investigation of iridium(III) complexes conjugated with ibuprofen.

The design and synthesis of a series of metal complexes formed by non-steroidal anti-inflammatory drugs (NSAIDs) ibuprofen (IBP) and iridium(III), with the molecular formula [Ir(C^N)2bpy(4-CH2OIBP-4'-CH2OIBP)](PF6) (Ir-IBP-1, Ir-IBP-2) (C^N = 2-phenylpyridine (ppy, Ir-IBP-1), 2-(2-thienyl)pyridine (thpy, Ir-IBP-2)) was introduced in this article. Firstly, it was found that the anti-proliferative activity of these complexes was more effective than that of cisplatin. Further research showed that Ir-IBP-1 and Ir-IBP-2 can accumulate in intracellular mitochondria, thereby disrupting mitochondrial membrane potential (MMP), increasing intracellular reactive oxygen species (ROS), blocking the G2/M phase of the cell cycle, and inducing cell apoptosis. In terms of protein expression, the expression of COX-2, MMP-9, NLRP3 and Caspase-1 proteins can be downregulated, indicating their ability to anti-inflammatory and overcome immune evasion. Furthermore, Ir-IBP-1 and Ir-IBP-2 can induce immunogenic cell death (ICD) by triggering the release of cell surface calreticulin (CRT), high mobility group box 1 (HMGB1) and adenosine triphosphate (ATP). Overall, iridium(III)-IBP conjugates exhibit various anti-tumor mechanisms, including mitochondrial damage, cell cycle arrest, inflammatory suppression, and induction of ICD.

Iridium(III) complexes conjugated with naproxen exhibit potent anti-tumor activities by inducing mitochondrial damage, modulating inflammation, and enhancing immunity.

A series of Ir(III)-naproxen (NPX) conjugates with the molecular formula [Ir(C^N)2bpy(4-CH2ONPX-4'-CH2ONPX)](PF6) (Ir-NPX-1-3) were designed and synthesized, including C^N = 2-phenylpyridine (ppy, Ir-NPX-1), 2-(2-thienyl)pyridine (thpy, Ir-NPX-2) and 2-(2,4-difluorophenyl)pyridine (dfppy, Ir-NPX-3). Cytotoxicity tests showed that Ir-NPX-1-3 exhibited excellent antitumor activity, especially in A549R cells. The cellular uptake experiment showed that the complexes were mainly localized in mitochondria, and induced apoptosis in A549R cells by damaging the structure and function of mitochondria. The main manifestations are a decrease in the mitochondrial membrane potential (MMP), an increase in reactive oxygen species (ROS) levels, and cell cycle arrest. Furthermore, Ir-NPX-1-3 could inhibit the migration and colony formation of cancer cells, demonstrating potential anti-metastatic ability. Finally, the anti-inflammatory and immunological applications of Ir-NPX-1-3 were verified. The downregulation of cyclooxygenase-2 (COX-2) and programmed death-ligand 1 (PD-L1) expression levels and the release of immunogenic cell death (ICD) related signaling molecules such as damage-associated molecular patterns (DAMPs) (cell surface calreticulin (CRT), high mobility group box 1 (HMGB1), and adenosine triphosphate (ATP)) indicate that these Ir(III) -NPX conjugates are novel ICD inducers with synergistic effects in multiple anti-tumor pathways.

Antifungal activity of ruthenium (II) complex combined with fluconazole against drug-resistant Candida albicans in vitro and its anti-invasive infection in vivo.

With the abuse of antibiotics and azoles, drug-resistant Candida albicans infections have increased sharply and are spreading rapidly, thereby significantly reducing the antifungal efficacy of existing therapeutics. Several patients die of fungal infections every year. Therefore, there is an urgent requirement to develop new drugs. Accordingly, we synthesized a series of polypyridyl ruthenium (II) complexes having the formula [Ru (NN)2 (bpm)] (PF6)2 (N-N = 2,2'-bipyridine) (bpy, in Ru1), 1,10-phenanthroline (phen, in Ru2), 4,7-diphenyl-1,10-phenanthroline (DIP, in Ru3) (bpm = 2,2'-bipyrimidine) and studied their antifungal activities. Ru3 alone had no effect on the drug-resistant strains, but Ru3 combined with fluconazole (FLC) exhibited significant antifungal activity on drug-resistant strains. A high-dose combination of Ru3 and FLC exhibited direct fungicidal activity by promoting the accumulation of reactive oxygen species and damaging the cellular structure of C. albicans. Additionally, the combination of Ru3 and FLC demonstrated potent antifungal efficacy in vivo in a mouse model of invasive candidiasis. Moreover, the combination significantly improved the survival state of mice, restored their immune systems, and reduced renal injury. These findings could provide ideas for the development of ruthenium (II) complexes as novel antifungal agents for drug-resistant microbial stains.

Ruthenium-Arene-ß-Carboline Complexes as Potent Inhibitors of Cyclin-Dependent Kinase 1: Synthesis, Characterization and Anticancer Mechanism Studies.

A series of Ru(II)-arene complexes (1-6) of the general formula [(η(6)-arene)Ru(L)Cl]PF6 (arene=benzene or p-cymene; L=bidentate ß-carboline derivative, an indole alkaloid with potential cyclin-dependent kinases (CDKs) inhibitory activities) is reported. All the complexes were fully characterized by classical analytical methods, and three were characterized by X-ray crystallography. Hydrolytic studies show that ß-carboline ligands play a vital role in their aqueous behaviour. These complexes are highly active in vitro, with the most active complex 6 displaying a 3- to 12-fold higher anticancer activity than cisplatin against several cancer cell lines. Interestingly, the complexes are able to overcome cross-resistance to cisplatin, and show much lower cytotoxicity against normal cells. Complexes 1-6 may directly target CDK1, because they can block cells in the G2M phase, down-regulate the expression of CDK1 and cyclin B1, and inhibit CDK1/cyclin B in vitro. Further mechanism studies show that the complexes can effectively induce apoptosis through mitochondrial-related pathways and intracellular reactive oxygen species (ROS) elevation.

Histone-deacetylase-targeted fluorescent ruthenium(II) polypyridyl complexes as potent anticancer agents.

Histone deacetylases inhibitors (HDACis) have gained much attention as a new class of anticancer agents in recent years. Herein, we report a series of fluorescent ruthenium(II) complexes containing N(1)-hydroxy-N(8)-(1,10-phenanthrolin-5-yl)octanediamide (L), a suberoylanilide hydroxamic acid (SAHA) derivative, as a ligand. As expected, these complexes show interesting chemiphysical properties, including relatively high quantum yields, large Stokes shifts, and long emission lifetimes. The in vitro inhibitory effect of the most effective drug, [Ru(DIP)2L](PF6)2 (3; DIP: 4,7-diphenyl-1,10-phenanthroline), on histone deacetylases (HDACs) is approximately equivalent in activity to that of SAHA, and treatment with complex 3 results in increased levels of the acetylated histone H3. Complex 3 is highly active against a panel of human cancer cell lines, whereas it shows relatively much lower toxicity to normal cells. Further mechanism studies show that complex 3 can elicit cell cycle arrest and induce apoptosis through mitochondria-related pathways and the production of reactive oxygen species. These data suggest that these fluorescent ruthenium(II)-HDACi conjugates may represent a promising class of anticancer agents for potential dual imaging and therapeutic applications targeting HDACs.

Cyclometalated iridium(III) complexes combined with fluconazole: antifungal activity against resistant C. albicans.

Candida albicans (C. albicans) is a ubiquitous clinical fungal pathogen. In recent years, combination therapy, a potential treatment method to overcome C. albicans resistance, has gained traction. In this study, we synthesized a series of cyclometalated iridium(III) complexes with the formula [Ir(C-N)2(tpphz)](PF6) (C-N = 2-phenylpyridine (ppy, in Ir1), 2-(2-thienyl)pyridine (thpy, in Ir2), 2-(2,4-difluorophenyl) pyridine (dfppy, in Ir3), tpphz = tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]phenazine) and polypyridyl ruthenium(II) complexes with the formula [Ru(N-N)2(tpphz)](PF6)2 (N-N = 2,2'-bipyridine (bpy, in Ru1), 1,10-phenanthroline (phen, in Ru2), 4,7-diphenyl-1,10-phenanthroline (DIP, in Ru3)), and investigated their antifungal activities against drug-resistant C. albicans and their combination with fluconazole (FLC). Of which, the combination of the lead iridium(III) complex Ir2 and FLC showed strong antifungal activity against drug-resistant C. albicans. Mechanism studies have shown that they can inhibit the formation of hyphae and biofilm, damage mitochondrial function and accumulate intracellular ROS. Therefore, iridium(III) complexes combined with FLC can be used as a promising treatment to exert anti-drug-resistant C. albicans activity, in order to improve the treatment efficiency of fungal infection.

Heteronuclear Ru(II)-Re(I) complexes as potential photodynamic anticancer agents with anti-metastatic and anti-angiogenic activities.

Herein, three heterometallic Ru(II)-Re(I) complexes, [Ru(NN)2(tpphz)Re(CO)3Cl](PF6)2 (N-N = 2,2'-bipyridine (bpy, in RuRe1), 1,10-phenanthroline (phen, in RuRe2), 4,7-diphenyl-1,10-phenanthroline (DIP, in RuRe3), tpphz = tetrapyrido[3,2-a:2',3'-c:3″,2″-h:2″',3″'-j]phenazine), using tpphz as a bridging ligand to connect Ru(II) polypyridyl moiety and Re(I) tricarbonyl moiety were designed and synthesized. Cytotoxicity tests revealed that RuRe1-3 exhibited high phototoxicities against several cancer cell lines tested, with IC50 values ranging from 0.8 to 6.8 µM. Notably, RuRe2 exhibited the most significant increase in cytotoxicity against human prostate cancer (PC3) cells under light (450 nm) irradiation, with phototoxicity index (PI) value increasing by >112.3-fold. Further mechanistic studies of RuRe2 revealed that RuRe2-mediated PDT could induce tumor cell apoptosis through the mitochondrial pathway. Moreover, RuRe2-mediated PDT could inhibit PC3 cell scratch healing and reduce the expression levels of matrix metalloproteinases 2 (MMP-2), matrix metalloproteinases 9 (MMP-9) and vascular endothelial growth factor receptor VEGFR2. Finally, angiogenic activity assays performed in human umbilical vein endothelial cells (HUVECs) showed that RuRe2 exerted an anti-angiogenesis effect. Our study demonstrated that RuRe1-3 were promising PDT antitumor agents with potential anti-metastatic and anti-angiogenic activities.

Novel heterobimetallic Ir(III)-Re(I) complexes: design, synthesis and antitumor mechanism investigation.

The reasonable design of binuclear or multinuclear metal complexes has demonstrated their potential advantages in the anticancer field. Herein, three heterobimetallic Ir(III)-Re(I) complexes, [Ir(C^N)2LRe(CO)3DIP](PF6)2 (C^N = 2-phenylpyridine (ppy, in IrRe-1), 2-(2-thienyl)pyridine (thpy, in IrRe-2) and 2-(2,4-difluorophenyl)pyridine (dfppy, in IrRe-3); L = pyridylimidazo[4,5-f][1,10]phenanthroline; DIP = 4,7-diphenyl-1,10-phenanthroline), were designed and synthesized. The heterobimetallic IrRe-1-3 complexes show pH-sensitive emission properties, which can be used for specific imaging of lysosomes. Additionally, IrRe-1-3 display higher cytotoxicity against tested tumor cell lines than the clinical chemotherapeutic drug cisplatin. Further mechanisms indicate that IrRe-1-3 can induce apoptosis and autophagy, increase intracellular reactive oxygen species (ROS), depolarize the mitochondrial membrane (MMP), block the cell cycle at the G0/G1 phase and inhibit cell migration. To the best of our knowledge, this is the first example of the synthesis of heterobimetallic Ir(III)-Re(I) complexes with superior anticancer activities and evaluation of their anticancer mechanisms.

Jatavaleridoids A-H, eight new iridoids from the roots and rhizomes of Valeriana jatamansi Jones.

Eight new iridoids, jatavaleridoids A-H (1-8), were isolated from the roots and rhizomes of Valeriana jatamansi. Their structures and absolute configurations were elucidated based on NMR and HRESIMS spectroscopic data, as well as quantum chemical calculation. Structurally, compounds 1-5 and 8 were rare iridoids with long-chain fatty acid esters at C-10. In addition, compound 7 showed cytotoxicity, while compounds 1 and 2 exhibited inhibition on NO production.

Lysosome-targeted cyclometalated iridium(III) complexes: JMJD inhibition, dual induction of apoptosis, and autophagy.

A series of cyclometalated iridium(III) complexes with the formula [Ir(C^N)2 L](PF6) (C^N = 2-phenylpyridine (ppy, in Ir-1), 2-(2-thienyl)pyridine (thpy, in Ir-2), 2-(2,4-difluorophenyl)pyridine (dfppy, in Ir-3), L = 2-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)quinolin-8-ol) were designed and synthesized, which utilize 8-hydroxyquinoline derivative as N^N ligands to chelate the cofactor Fe2+ of the Jumonji domain-containing protein (JMJD) histone demethylase. As expected, the results of UV/Vis titration analysis confirm the chelating capabilities of Ir-1-3 for Fe2+, and molecular docking studies also show that Ir-1-3 can interact with the active pocket of JMJD protein, and treatment of cells with Ir-1-3 results in significant upregulation of trimethylated histone 3 lysine 9 (H3K9Me3), indicating the inhibition of JMJD activity. Meanwhile, Ir-1-3 exhibit much higher cytotoxicity against the tested tumor cell lines compared with the clinical chemotherapeutic agent cisplatin. And Ir-1-3 can block the cell cycle at the G2/M phase and inhibit cell migration and colony formation. Further studies show that Ir-1-3 can specifically accumulate in lysosomes, damage the integrity of lysosomes, and induce apoptosis and autophagy. Reduction of mitochondrial membrane potential and elevation of reactive oxygen species also contribute to the antitumor effects of Ir-1-3. Finally, Ir-1 can inhibit tumor growth effectively in vivo and increase the expression of H3K9Me3 in tumor tissues. Our study demonstrates that these iridium(III) complexes are promising anticancer agents with multiple functions, including the inhibition of JMJD and induction of apoptosis and autophagy.

Phosphorescent rhenium(I) complexes conjugated with artesunate: Mitochondrial targeting and apoptosis-ferroptosis dual induction.

Cell death is essential for cancer, which can be induced through multiple mechanisms. Ferroptosis, a newly emerging form of non-apoptotic cell death, involves the generation of iron-dependent reactive oxygen species (ROS). In this study, we designed and synthesized two artesunate (ART) conjugated phosphorescent rhenium(I) complexes (Re(I)-ART conjugates), [Re(N^N)(CO)3(PyCH2OART)](PF6) (Re-ART-1 and Re-ART-2) (Py = pyridine, N^N = 1,10-phenanthroline (phen, in Re-ART-1) and 4,7-diphenyl-1,10-phenanthroline (DIP, in Re-ART-2)) that can specifically locate in the mitochondria of human cervical carcinoma (HeLa). Mechanism studies show that Re-ART-1 and Re-ART-2 exhibit high cytotoxicity against cancer cells lines and can induce both apoptosis and ferroptosis in HeLa cells through mitochondrial damage, caspase cascade, glutathione (GSH) depletion, glutathione peroxidase 4 (GPX4) inactivation and lipid peroxidation accumulation. As a result, this work presents the rational design of Re(I)-ART conjugates as a promising strategy to induce both apoptosis and ferroptosis and improve therapeutic efficiency of cancer treatment.

3-Bromo-4-dibenzyl-amino-5-methoxy-furan-2(5H)-one.

In the the title compound, C(19)H(18)BrNO(3), the furan-one ring is almost planar [maximum atomic deviation = 0.019 (3) Å] and is nearly perpendicular to the two phenyl rings, making dihedral angles of 88.96 (17) and 87.71 (17)°. Inter-molecular C-H⋯O hydrogen bonding is present in the crystal structure.

Mitochondria-targeted artesunate conjugated cyclometalated iridium(iii) complexes as potent anti-HepG2 hepatocellular carcinoma agents.

Hepatocellular carcinoma (HCC) poses a serious threat to people's health worldwide. Artesunate (ART), one of the classical antimalarial drugs, has recently been shown to exert significant cytotoxicity in various cancers, but its bioavailability is low. Cyclometalated iridium(iii) complexes have emerged as a promising class of anticancer therapeutic agents. Herein, through conjugation of two of them, three novel Ir(iii)-ART conjugates, [Ir(C-N)2(bpy-ART)](PF6) (bpy = 2,2'-bipyridine, C-N = 2-phenylpyridine (ppy, Ir-ART-1), 2-(2-thienyl)pyridine (thpy, Ir-ART-2), and 2-(2,4-difluorophenyl)pyridine (dfppy, Ir-ART-3)) have been synthesized, and their potential as anti-HCC agents was evaluated. We demonstrate that Ir-ART-1-3 display higher cytotoxicity against HCC cell lines than normal liver cells, and they can especially locate to mitochondria of HepG2 cells and induce a series of mitochondria-mediated apoptosis events. Moreover, Ir-ART-1-3 can regulate the cell cycle and inhibit metastasis of HepG2 cells. Finally, in vivo antitumor evaluation also demonstrates the inhibitory activity of Ir-ART-1 on tumor growth. Taken together, these Ir(iii)-ART conjugates have the potential to become drug candidates for future anti-HCC treatments.

Identification of two mitochondrial-targeting cyclometalated iridium(III) complexes as potent anti-glioma stem cells agents.

Glioma stem cells (GSCs) are thought to be responsible for the recurrence and invasion of glioblastoma multiform (GBM), which have been evaluated and exploited as the therapeutic target for GBM. Cyclometalated iridium(III) complexes have been demonstrated as the potential anticancer agents, however, their antitumor efficacies against GSCs are still unknown. Herein, we investigated the antitumor activity of two cyclometalated iridium(III) complexes [Ir(ppy)2L](PF6) (Ir1) and [Ir(thpy)2L](PF6) (Ir2) (ppy = 2-phenylpyridine, thpy = 2-(2-thienyl)pyridine and L = 4,4'-Bis(hydroxymethyl)-2,2'-bipyridine) against GSCs. The results clearly indicate that Ir1 and Ir2 kill GSCs selectively with IC50 values ranging from 5.26-9.05 µM. Further mechanism research display that Ir1 and Ir2 can suppress the proliferation of GSCs, penetrate into GSCs efficiently, localize to mitochondria, and induce mitochondria-mediated apoptosis, including the loss of mitochondrial membrane (MMP), elevation of intracellular reactive oxygen species (ROS) and caspases activation. Moreover, Ir1 and Ir2 can destroy the GSCs self-renewal and unlimited proliferation capacity by affecting the GSCs colony formation. According our knowledge, this is the first study to investigate the anti-GSCs properties of cyclometalated iridium(III) complexes.

Tumor-targeted supramolecular nanoparticles self-assembled from a ruthenium-ß-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 αvß3-rich tumor cells with high selectivity. This strategy presents new opportunities for the construction of tumor-targeting metallo-anticancer therapeutics.