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The opportunistic human pathogen Pseudomonas aeruginosa (P. aeruginosa) poses a significant threat to human health, causing sepsis, inflammation, and pneumonia, so it is crucial to devise an expeditious detection platform for the P. aeruginosa. In this work, bis (2- (3, 5- dimethylphenyl) quinoline- C2, N') (acetylacetonato) iridium (III) Ir (dmpq) 2 (acac) with excellent electrochemiluminescence (ECL) and fluorescence (FL) and magnetic nanoparticles were encapsulated in silica spheres. The luminescent units exhibited equal ECL and FL properties compared with single iridium complexes, and enabled rapid separation, which was of vital significance for the establishment of biosensors with effective detection. In addition, the luminescent units were further reacted with the DNA with quenching units to obtain the signal units, and the ECL/FL dual-mode biosensor was employed with the CRISPR/Cas12a system to further improve its specific recognition ability. The ECL detection linear range of as-proposed biosensor in this work was 100 fM-10 nM with the detection limit of 73 fM (S/N = 3), and FL detection linear range was 1 pM-10 nM with the detection limit of 0.126 pM (S/N = 3). Importantly, the proposed dual-mode biosensor exhibited excellent repeatability and stability in the detection of P. aeruginosa in real samples, underscoring its potential as an alternative strategy for infection prevention and safeguarding public health and safety in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Lactate-enriched tumor microenvironment (TME) fosters an immunosuppressive milieu to hamper the functionality of tumor-associated macrophages (TAMs). However, tackling the immunosuppressive effects wrought by lactate accumulation is still a big challenge. Herein, we construct a dual enzyme-driven cascade reaction platform (ILH) with immunosuppressive TME modulation for photoacoustic (PA) imaging-guided catalytic therapy and immune activation. The ILH is composed of iridium (Ir) metallene nanozyme, lactate oxidase (LOx), and hyaluronic acid (HA). The combination of Ir nanozyme and LOx can not only efficiently consume lactate to reverse the immunosuppressive TME into an immunoreactive one by promoting the polarization of TAMs from the M2 to M1 phenotype, thus enhancing antitumor defense, but also alleviate tumor hypoxia as well as induce strong oxidative stress, thus triggering immunogenic cell death (ICD) and activating antitumor immunity. Furthermore, the photothermal performance of Ir nanozyme can strengthen the cascade catalytic ability and endow ILH with a PA response. Based on the changes in PA signals from endogenous molecules, three-dimensional multispectral PA imaging was utilized to track the process of cascade catalytic therapy in vivo. This work provides a nanoplatform for dual enzyme-driven cascade catalytic therapy and immune activation by regulating the immunosuppressive TME.

In an effort to develop hypoxia-active iridium(III) complexes with long visible-light absorption, we synthesized and characterized five bis(terpyridine) Ir(III) complexes bearing oligothienyl substituents on one of the terpyridine ligands, i.e., n T-Ir ( n = 0-4). The UV-vis absorption, emission, and transient absorption spectroscopy were employed to characterize the singlet and triplet excited states of these complexes and to explore the effects of varied number of thienyl units on the photophysical parameters of the complexes. In vitro photodynamic therapeutic activities of these complexes were assessed with respect to three melanoma cell lines (SKMEL28, A375, and B16F10) and two breast cancer cell lines (MDA-MB-231 and MCF-7) under normoxia (∼18.5% oxygen tension) and hypoxia (1% oxygen tension) upon broadband visible (400-700 nm), blue (453 nm), green (523 nm), and red (633 nm) light activation. It was revealed that the increased number of thienyl units bathochromically shifted the low-energy absorption bands to the green/orange spectral regions and the emission bands to the near-infrared (NIR) regions. The lowest triplet excited-state lifetimes and the singlet oxygen generation efficiency also increased from 0T to 2T substitution but decreased in 3T and 4T substitution. All complexes exhibited low dark cytotoxicity toward all cell lines, but 2T-Ir-4T-Ir manifested high photocytotoxicity for all cell lines upon visible, blue, and green light activation under normoxia, with 2T-Ir showing the strongest photocytotoxicity toward SKMEL28, MDA-MB-231, and MCF-7 cells, and 4T-Ir being the most photocytotoxic one for B16F10 and A375 cells. Singlet oxygen, superoxide anion radicals, and peroxynitrite anions were found to likely be involved in the photocytotoxicity exhibited by the complexes. 4T-Ir also showed strong photocytotoxicity upon red-light excitation toward all cell lines under normoxia and retained its photocytotoxicity under hypoxia toward all cell lines upon visible, blue, and green light excitation. The hypoxic activity of 4T-Ir along with its green to orange light absorption, NIR emission, and low dark cytotoxicity suggest its potential as a photosensitizer for photodynamic therapy applications.

Reactive oxygen species (ROS)-dependent monotherapy usually demonstrates poor therapeutic outcomes, due to the accompanied activation of protective autophagy in tumor cells, which results in ROS tolerance and immune suppression. In this study, a bimetallic electro-sensitizer, Pt-Ir NPs is constructed, loaded with the autophagy inhibitor chloroquine (Pt-Ir-CQ NPs), to enhance the effectiveness of electrotherapy by inhibiting autophagy and activating anti-tumor immune responses. This novel electrotherapy platform demonstrates unique advantages, particularly in the treatment of hypoxic and immunosuppressive tumors. First, the electro-sensitizer catalyzes water molecules into ROS under electric field, achieving tumor ablation through electrotoxicity. Second, the incorporated CQ inhibits the protective autophagy induced by electrotherapy, restoring the sensitivity of tumor cells to ROS and thereby enhancing the anti-tumor effects of electrotherapy. Third, Pt-Ir-CQ NPs enhance the functionality of antigen-presenting cells and immunogenic cells through inhibiting autophagy, synergistically activating the anti-tumor immune responses along with the immunogenic cell death (ICD) effect induced by electrotherapy. This study provides a novel approach for the effective ablation and long-term inhibition of solid tumors through flexible modulation by an exogenous electric field., (© 2024 Wiley‐VCH GmbH.)

Polymer-metal complexes (PMCs) based on poly(2,2'-bipyridine-4,4'-dicarboxamide-co-polydimethylsiloxanes) with cyclometalated di(2-phenylpyridinato-C 2 ,N')iridium(III) fragments and cross-linked by Zn 2+ (Zn[Ir]-BipyPDMSs) or Ir 3+ (Ir[Ir]-BipyPDMSs) represent flexible, stretchable, phosphorescent, and self-healing molecular oxygen sensors. PMCs provide strong phosphorescence at λ em = 595-605 nm. Zn[Ir]-BipyPDMS with PDMS chain length of M n = 5000 has the highest quantum yield of 9.3% and is a molecular oxygen sensor at different O 2 concentrations (0-100 vol%) compared to Ir[Ir]-BipyPDMSs. A Stern-Volmer constant is determined for Zn[Ir]-BipyPDMS as K SV = 0.014% -1 , which is similar to the reported oxygen-sensitive iridium(III) complexes. All synthesized PMCs exhibit high elongation at break (up to 1100%) and self-healing efficiency (up to 99%)., (© 2024 Wiley‐VCH GmbH.)

An ideal tumor treatment strategy involves therapeutic approaches that can enhance the immunogenicity of the tumor microenvironment while simultaneously eliminating the primary tumor. A cholic acid-modified iridium(III) (Ir3) photosensitizer, targeted to the endoplasmic reticulum (ER), has been reported to exhibit potent type I and type II photodynamic therapeutic effects against triple-negative breast cancer (MDA-MB-231). This photosensitizer induces pyroptotic cell death mediated by gasdermin E (GSDME) through photodynamic means and enhances tumor immunotherapy. Mechanistic studies have revealed that complex Ir3 induces characteristics of damage-related molecular patterns (DAMPs) in MDA-MB-231 breast cancer cells under light conditions. These include cell-surface calreticulin (CRT) eversion, extracellular high mobility group box 1 (HMGB1) and ATP release, accompanied by ER stress and increased reactive oxygen species (ROS). Consequently, complex Ir3 promotes dendritic cell maturation and antigen presentation under light conditions, fully activates T cell-dependent immune response in vivo, and ultimately eliminates distant tumors while destroying primary tumors. In conclusion, immune regulation and targeted intervention mediated by metal complexes represent a new and promising approach to tumor therapy. This provides an effective strategy for the development of combined targeted therapy and immunotherapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The development of novel catalyst with high catalytic activity is important for electrochemical non-enzymatic glucose sensing. Here, iridium single-atom/nickel oxide nanoparticle/N-doped graphene nanosheet (Ir 1 /NiO/NG) with the loading of 1.13 wt% Ir was successfully synthesized for constructing electrochemical non-enzymatic glucose sensor for the first time. The morphology and structure of Ir 1 /NiO/NG were characterized by XRD, SEM, TEM, HRTEM, and XPS, and the presence of Ir SAs was confirmed by AC-HAADF-STEM. The Ir 1 /NiO/NG shows 65 mV lower oxidation potential and 3.3 times higher response current than Ni(OH) 2 /NG. In addition, Ir 1 /NiO/NG exhibits high sensitivity (70.09 μA mM -1 cm -2 ), excellent selectivity, low detection limit (2.00 μM), and great stability (91.53% current remaining after 21 days) for electrochemical non-enzymatic glucose sensing. The outstanding catalytic and sensing performance of Ir 1 /NiO/NG is mainly attributed to synergistic effect of Ir SAs, NiO nanoparticles, and highly conductive NG, which modulate the electronic and geometric structure of Ir 1 /NiO/NG. This work shows the promising potential of SACs in electrochemical sensing., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

The enzyme-like activity of noble metal nanomaterials has been widely demonstrated. However, as an important noble metal, iridium (Ir) and its alloy nanomaterials have been less studied, particularly regarding the effect of Ir content on enzyme-like activity. Here, we demonstrated for the first time that a low Ir content can greatly improve the peroxidase-like activity of Pt-based nanozymes. When the weight percentage of Ir was 3.45% in trimetallic PtAuIr hollow nanorods (HNRs) and 2.86% in bimetallic PtIr HNRs, their specific activity increased by approximately 70% compared to their PtAu and Pt counterparts, respectively. However, a slightly higher percentage of Ir significantly diminished the enhancement effect on their specific activity. Density functional theory (DFT) calculations show that the rate-determining step (RDS) energy barrier of the nanozyme with low Ir content is lower than that of the nanozyme with slightly higher Ir content. Furthermore, we studied the kinetic properties of the PtAuIr nanozyme using TMB as the substrate. Its Michaelis-Menten constant ( K m ) and V max were 1.756 mM and 2.152 × 10 -6 M s -1 , respectively. Additionally, a colorimetric detection platform based on the PtAuIr nanozyme was established and applied to detect o -phenylenediamine (OPD), with a detection limit as low as 0.076 μM. This study highlights the important role of the Ir content in Pt-based nanozymes and demonstrates that PtAuIr nanozymes have potential applications in environmental detection.

Two-photon photodynamic therapy (TP-PDT) has become a major cancer treatment due to its larger tissue penetration depth, good spatial selectivity, and less damage to normal cells. In this contribution, a series of novel photosensitizer molecules ( Ir-2 , Ir-2-1 ∼ Ir-2-4 ) have been designed based on the experimentally demonstrated photosensitizer [Ir(ppy) 2 (osip)] (PF 6 ) by fine tuning the π-conjugated structure and introducing different nitrogen-heterocyclic substituents. The electronic structures, one- and two-photon absorption spectra, triplet excited state lifetime, solvation-free energy, and photosensitizing performance were evaluated by means of density functional theory (DFT) and time-dependent density functional theory (TDDFT). The results suggested that the molecule Ir-2 , incorporating thiophene as the π-connecting group, exhibits a higher probability of triplet state formation, enhanced two-photon absorption cross-section, and prolonged triplet state lifetime. Furthermore, the four designed nitrogen-heterocyclic complexes Ir-2-1 ∼ Ir-2-4 demonstrate favorable photosensitizing properties, with two-photon absorption cross-sections reaching up to 110 GM and triplet excited state lifetimes exceeding 1000 μs for Ir-2-4 .

Real-time visualization of metabolic processes in vivo provides crucial insights into conditions like cancer and metabolic disorders. Metabolic magnetic resonance imaging (MRI), by amplifying the signal of pyruvate molecules through hyperpolarization, enables non-invasive monitoring of metabolic fluxes, aiding in understanding disease progression and treatment response. Signal Amplification By Reversible Exchange (SABRE) presents a simpler, cost-effective alternative to dissolution dynamic nuclear polarization, eliminating the need for expensive equipment and complex procedures. We present the first in vivo demonstration of metabolic sensing in a human pancreatic cancer xenograft model compared to healthy mice. A novel perfluorinated Iridium SABRE catalyst in a fluorinated solvent and methanol blend facilitated this breakthrough with a 1.2-fold increase in [1- 13 C]pyruvate SABRE hyperpolarization. The perfluorinated moiety allowed easy separation of the heavy-metal-containing catalyst from the hyperpolarized [1- 13 C]pyruvate target. The perfluorinated catalyst exhibited recyclability, maintaining SABRE-SHEATH activity through subsequent hyperpolarization cycles with minimal activity loss after the initial two cycles. Remarkably, the catalyst retained activity for at least 10 cycles, with a 3.3-fold decrease in hyperpolarization potency. This proof-of-concept study encourages wider adoption of SABRE hyperpolarized [1- 13 C]pyruvate MR for studying in vivo metabolism, aiding in diagnosing stages and monitoring treatment responses in cancer and other diseases., (© 2024 Wiley-VCH GmbH.)

Histidine (His) is a semi-essential amino acid and a unique key neurotransmitter involved in numerous physiological processes. An excessive or deficient amount of His in the body can lead to various related diseases. However, since the chemical structures of L-His and its metabolites (such as histamine (Ha), imidazole-4-acetate (ImA), etc. ) are very similar, simple and efficient selective detection of L-His and its related metabolites is of great importance but remains a great challenge. Herein, we successfully designed and synthesized a DMSO-assisted iridium(III) complex (Ir1-DMSO), which can be applied as a "turn-on" photoluminescence (PL) probe for the selective detection and quantification of L-His/Ha. More importantly, Ir1-DMSO exhibited good sensitivity, high selectivity, and anti-interference capability for L-His/Ha/His-containing proteins, which is advantageous due to its simple fabrication and low technical demands. This was attributed to the reaction of Ir1-DMSO with imidazole and amino groups of L-His/Ha. Furthermore, we show the utility of Ir1-DMSO as a PL imaging agent in cultures of E. coli and S. aureus . Considering its diversity of composition and structural flexibility, it can be extended to other solvents and Ir-ligand complexes for various analyses based on specific molecular recognition sensing platforms.

Hemostasis, infection, oxidative stress, and inflammation still severely impede the wound repair process. It is significant to develop multifunctional wound dressings that can function as needed in various stages of wound healing. In this study, iridium nanoparticles (IrNPs) with multi-enzyme mimetic activity were complexed with chitosan (CS) and fucoidan (FD) for the first time to make a multifunctional CS/FD/IrNPs hydrogel with excellent antioxidant effect. The hydrogel has excellent physicochemical properties. In particular, the incorporation of IrNPs imparts excellent antioxidant properties to the hydrogel, which could scavenge reactive oxygen species (ROS). In addition, the hydrogel shows excellent hemostatic and antibacterial properties. The CS/FD/IrNPs hydrogel performs fast and efficient hemostasis in 21 s. Moreover, the blood loss of the CS/FD/IrNPs hydrogel group was approximately 10% of that in the control group and the antibacterial rate of CS/FD/IrNPs hydrogel against E. coli and S. aureus was up to 95 %. In vivo results demonstrate that CS/FD/IrNPs hydrogel promotes wound healing by attenuating ROS levels, reducing oxidative damage, mitigating inflammation, and accelerating angiogenesis. To summarize, the CS/FD/IrNPs hydrogel system, with hemostatic, antibacterial, antioxidant, anti-inflammatory and pro-healing activities, can be a promising and effective strategy for the treatment of clinically difficult-to-heal wounds., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest or personal relationships with this work., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Despite advances in Ir(III) and Ru(II) photosensitizers (PSs), their lack of selectivity for cancer cells has hindered their use in photodynamic therapy (PDT). We disclose the synthesis and characterization of two pairs of Ir(III) and Ru(II) polypyridyl complexes bearing two β-carboline ligands (N^N') functionalized with -COOMe ( L1 ) or -COOH ( L2 ), resulting in PSs of formulas [Ir(C^N) 2 (N^N')]Cl ( Ir-Me: C^N = ppy, N^N' = L1 ; Ir-H: C^N = ppy, N^N' = L2 ) and [Ru(N^N) 2 (N^N')](Cl) 2 ( Ru-Me: N^N = bpy, N^N' = L1; Ru-H: N^N = bpy, N^N' = L2 ). To enhance their selectivity toward cancer cells, Ir-H and Ru-H were coupled to a bombesin derivative ( BN3 ), resulting in the metallopeptides Ir-BN and Ru-BN . Ir(III) complexes showed higher anticancer activity than their Ru(II) counterparts, particularly upon blue light irradiation, but lacked cancer cell selectivity. In contrast, Ir-BN and Ru-BN exhibited selective photocytoxicity against prostate cancer cells, with a lower effect against nonmalignant fibroblasts. All compounds generated ROS and induced severe mitochondrial toxicity upon photoactivation, leading to apoptosis. Additionally, the ability of Ir-Me to oxidize NADH was demonstrated, suggesting a mechanism for mitochondrial damage. Our findings indicated that the conjugation of metal PSs with BN3 creates efficient PDT agents, achieving selectivity through targeting bombesin receptors and local photoactivation.

Three iridium(III) triazolato complexes of the general formula [Ir(triazolato R,R' )(ppy)(terpy)]PF 6 with ppy=2-phenylpyridine and terpy=2,2':6',2''-terpyridine were efficiently prepared by iClick reaction of [Ir(N 3 )(ppy)(terpy)]PF 6 , with alkynes and alkynones, which allowed facile introduction of biological carriers such as biotin and cholic acid. In contrast to the precursor azido complex, which decomposed upon photoexcitation on a very short time scale, the triazolato complexes were stable in solution for up to 48 h. They emit in the spectral region around 540 nm with a quantum yield of 15-35 % in aerated acetonitrile solution and exhibit low cytotoxicity with IC 50 values >50 μM for most complexes in L929 and HeLa cells, demonstrating their high suitability as luminescent probes. Cell uptake studies with confocal luminescence microscopy in prokaryotic Gram-positive S. aureus and Gram-negative E. coli bacteria as well as eukaryotic mammalian L929 and HeLa cells showed significant uptake in particular of the cholic acid conjugates iridium(III) moiety and distinct intracellular distribution modulated by the nature of the peripheral functional groups that can easily be modified by the iClick reaction., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

Cytochrome P450 3A4 (CYP3A4) is a crucial enzyme in human drug metabolism. To garner photochemical control over the inhibition of CYP3A4, a potent Ir(III)-based inhibitor of CYP3A4 was complexed with two Ru(II)-based photocaging groups. Chemical, photochemical, and biological properties of the photocaged inhibitors were characterized. Importantly, mixed Ru(II)-Ir(III) complexes strongly absorb green light, which facilitates the photochemical release of the Ir(III) inhibitor from the Ru(II) caging fragment [Ru(tpy)(Me 2 bpy)] 2+ , where tpy = 2,2':6',2″-terpyridine and Me 2 bpy = 6,6'-dimethyl-2,2'-bipyridine. Emission turn on, type II heme binding, and more potent inhibition under light vs dark conditions were observed. The study also demonstrated that a Ru(II)-Ir(III) conjugate can be photoactivated to exert cytotoxic effects on MCF-7 breast cancer cells upon green light exposure. Additionally, a synthesized analogue with one [Ru(TPA)] 2+ fragment (TPA = tris(pyridin-2-ylmethyl)amine) and two Ir(III) centers, although resistant to photochemical release, showed strong inhibition of CYP3A4 both in purified form and in CYP3A4-overexpressing HepG2 cells, with nanomolar potency. These mixed Ru(II)-Ir(III) compounds can permeate cell membranes and inhibit CYP3A4, presenting a new class of bioactive compounds.

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 < λ em  < 720 nm), with the Ru(II) derivatives displaying higher photoluminescence quantum yields and longer excited state lifetimes. The Ir PSs display pK a values between 5.9 and 7.9, whereas their Ru counterparts are less acidic (pK a > 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 (T 1  =  3 LC) 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 IC 50 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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Mononuclear phosphinite Iridium complexes based on ferrocene group have been prepared and characterized by various spectroscopic techniques. The complexes were subjected to cyclic voltammetry studies in order to determine the energies of HOMO and LUMO levels and to estimate their electrochemical and some electronic properties. Organic complex-based memory substrates were immobilized using TiO 2 -modified ITO electrodes, and the memory functions of phosphinite-based organic complexes were verified by chronoamperometry (CA) and open-circuit potential amperometry (OCPA). Extensive theoretical and experimental investigations were directed to gain a more profound understanding of the chemical descriptors and the diverse electronic transitions taking place within the iridium complexes, as well as their electrochemical characteristics. The quantum chemical calculations were carried out for the iridium complexes at the DFT/CAM-B3LYP level of theory in the gas phase. Furthermore, the antioxidant, antimicrobial, DNA binding, and DNA cleavage activities of the complexes were tested. Complex 2 exhibited the highest radical scavenging activity (67.5 ± 2.24 %) at 200.0 mg/L concentration. It was observed that the complexes formed an inhibition zone in the range of 8-15 mm against Gram + bacteria and in the range of 0-13 mm against Gram - bacteria. The agarose gel electrophoresis method was used to determine the DNA binding and DNA cleavage activities of the complexes. All of the tested complexes had DNA binding activity; however, complexes 1, 2, and 8 showed better binding activity than the others., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Medical applications of iridium (III) complexes include their use as state-of-the-art theranostic agents - molecules that combine therapeutic and diagnostic functions into a single entity. These complexes offer a promising avenue in medical diagnostics, precision imaging at single-cell resolution and targeted anticancer therapy due to their unique properties. In this review we report a short summary of their application in medical diagnostics, imaging at single-cell level and targeted anticancer therapy. The exceptional photophysical properties of Iridium (III) complexes, including their brightness and photostability, make them excellent candidates for bioimaging. They can be used to image cellular processes and the microenvironment within single cells with unprecedented clarity, aiding in the understanding of disease mechanisms at the molecular level. Moreover the iridium (III) complexes can be designed to selectively target cancer cells,. Upon targeting, these complexes can act as photosensitizers for photodynamic therapy (PDT), generating reactive oxygen species (ROS) upon light activation to induce cell death. The integration of diagnostic and therapeutic capabilities in Iridium (III) complexes offers the potential for a holistic approach to cancer treatment, enabling not only the precise eradication of cancer cells but also the real-time monitoring of treatment efficacy and disease progression. This aligns with the goals of personalized medicine, offering hope for more effective and less invasive cancer treatment strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

New iridium(III) compounds (C 1 -C 3 ) bearing 2-(1H-benzimidazol-2-yl)quinoline ligands with different side groups (benzyl, 2,3,4,5,6-pentamethylbenzyl and 2,3,4,5,6-pentafluorobenzyl) were synthesized and characterized by using spectroscopic analyses. The effects of different side groups of iridium compounds on the photophysical and electrochemical properties have been investigated. The cytotoxicity and apoptosis of the compounds have been evaluated on breast cancer cell lines using various methods including MTT assay, flow cytometry, qRT-PCR, and colony formation. The cytotoxicity of C 1 , expressed as IC50 values, was found to be 11.76 μM for MDA-MB-231 and 5.35 μM for MCF-7 cells. For C 3 , the IC50 value was 16.22 μM for MDA-MB-231 and 8.85 μM for MCF-7 cells. In both cell lines, increased levels of Bax and caspase 3, along with downregulation of BCL-2 and positive annexin V staining, were observed, confirming apoptosis. Moreover, the colony-forming abilities in both cell lines decreased after C 1 and C 3 complex treatment. All these results suggest that the compounds C 1 and C 3 may have potential in the treatment of breast cancer, though further research is needed to confirm their efficacy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Cigdem Sahin reports financial support was provided by Istanbul Medeniyet University. Sevki Arslan reports financial support was provided by Istanbul Medeniyet University. Rafet Kilincarslan reports financial support was provided by Pamukkale University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

For cancer metastasis inhibition, the combining of nanozymes with immune checkpoint blockade (ICB) therapy remains the major challenge in controllable reactive oxygen species (ROS) generation for creating effective immunogenicity. Herein, new nanozymes with light-controlled ROS production in terms of quantity and variety are developed by conjugating supramolecular-wrapped Fe single atom on iridium metallene with lattice-strained nanoislands (FeSA-Ir@PF NSs). The Fenton-like catalysis of FeSA-Ir@PF NSs effectively produced •OH radicals in dark, which induced ferroptosis and apoptosis of cancer cells. While under second near-infrared (NIR-II) light irradiation, FeSA-Ir@PF NSs showed ultrahigh photothermal conversion efficiency (𝜂, 75.29%), cooperative robust •OH generation, photocatalytic O 2 and 1 O 2 generation, and caused significant pyroptosis of cancer cells. The controllable ROS generation, sequential cancer cells ferroptosis and pyroptosis, led 99.1% primary tumor inhibition and multi-immunogenic responses in vivo. Most importantly, the inhibition of cancer lung metastasis is completely achieved by FeSA-Ir@PF NSs with immune checkpoint inhibitors, as demonstrated in different mice lung metastasis models, including circulating tumor cells (CTCs) model. This work provided new inspiration for developing nanozymes for cancer treatments and metastasis inhibition., (© 2024 Wiley‐VCH GmbH.)

Anticancer activity has been extensively studies. In this article, three ligands 2-(6-bromobenzo[d][1,3]dioxol-5-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (BDIP), 2-(7-methoxybenzo[d][1,3]dioxol-5-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (MDIP), 2-(6-nitrobenzo[d][1,3]dioxol-5-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (NDIP) and their iridium(III) complexes: [Ir(ppy) 2 (BDIP)](PF 6 ) (ppy = deprotonated 2-phenylpyridine, 3a), [Ir(ppy) 2 (MDIP)](PF 6 ) (3b) and [Ir(ppy) 2 (NDIP)](PF 6 ) (3c) were synthesized. The cytotoxicity of 3a, 3b, 3c against Huh7, A549, BEL-7402, HepG2, HeLa, and non-cancer NIH3T3 was tested using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. The results obtained from the MTT test stated clearly that these complexes demonstrated moderate or non-cytotoxicity toward Huh7, BEL-7402, HepG2 and HeLa except A549 cells. To improve the anticancer efficacy, we used white light to irradiate the mixture of cells and complexes for 30 min, the anticancer activity of the complexes was greatly enhanced. Particularly, 3a and 3b exhibited heightened capability to inhibit A549 cells proliferation with IC 50 (half maximal inhibitory concentration) values of 0.7 ± 0.3 μM and 1.8 ± 0.1 μM, respectively. Cellular uptake has shown that 3a and 3b can be accumulated in the cytoplasm. Wound healing and colony forming showed that 3a and 3b significantly hinder the cell migration and growth in the S phase. The complexes open mitochondrial permeability transition pore (MPTP) channel and cause the decrease of membrane potential, release of cytochrome C, activation of caspase 3, and finally lead to apoptosis. In addition, 3a and 3b cause autophagy, increase the lipid peroxidation and lead to ferroptosis. Also, 3a and 3b increase the expression of calreticulin (CRT), high mobility group box 1 (HMGB1), heat shock protein 70 (HSP70), thereby inducing immunogenic cell death., Competing Interests: Declaration of competing interest The authors declare no competing interest exists., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Recent breakthroughs in cancer immunology have propelled immunotherapy to the forefront of cancer research as a promising treatment approach that harnesses the body's immune system to effectively identify and eliminate cancer cells. In this study, three novel cyclometalated Ir(III) complexes, Ir1, Ir2, and Ir3, were designed, synthesized, and assessed in vitro for cytotoxic activity against several tumor-derived cell lines. Among these, Ir1 exhibited the highest cytotoxic activity, with an IC 50 value of 0.4 ± 0.1 μM showcasing its significant anticancer potential. Detailed mechanistic analysis revealed that co-incubation of Ir1 with 143B cells led to Ir1 accumulation within mitochondria and the endoplasmic reticulum (ER). Furthermore, Ir1 induced G0/G1 phase cell cycle arrest, while also diminishing mitochondrial membrane potential, disrupting mitochondrial function, and triggering ER stress. Intriguingly, in mice the Ir1-induced ER stress response disrupted calcium homeostasis to thereby trigger immunogenic cell death (ICD), which subsequently activated the host antitumor immune response while concurrently dampening the in vivo tumor-induced inflammatory response., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The decline of antibiotics efficacy worldwide has recently reached a critical point urging for the development of new strategies to regain upper hand on multidrug resistant bacterial strains. In this context, the raise of photodynamic therapy (PDT), initially based on organic photosensitizers (PS) and more recently on organometallic PS, offers promising perspectives. Many PS exert their biological effects through the generation of reactive oxygen species (ROS) able to freely diffuse into and to kill surrounding bacteria. Hijacking of the bacterial iron-uptake systems with siderophore-PS conjugates would specifically target pathogens. Here, we report the synthesis of unprecedented conjugates between the siderophore desferrioxamine B (DFOB) and an antibacterial iridium(III) PS. Redox properties of the new conjugates have been determined at excited states and compared to that of an antibacterial iridium PS previously reported by our groups. Tested on nosocomial pathogen Pseudomonas aeruginosa and other bacteria, these conjugates demonstrated significant inhibitory activity when activated with blue LED light. Ir(III) conjugate and iridium free DFOB-2,2'-dipyridylamine ligands were crystallized in complex with FoxA, the outer membrane transporter involved in DFOB uptake in P. aeruginosa and revealed details of the binding mode of these unprecedented conjugates., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Vibrio parahaemolyticus (V. parahaemolyticus) is a major foodborne pathogen, which can cause serious foodborne illnesses like diarrhoea. Rapid on-site detection of foodborne pathogens is an ideal way to respond to foodborne illnesses. Herein, we provide an electrochemical sensor for rapid on-site detection. This sensor utilized a pH-sensitive metal-oxide material for the concurrent isothermal amplification and label-free detection of nucleic acids. Based on a pH-sensitive hydrated iridium oxide oxyhydroxide film (HIROF), the electrode transforms the hydrogen ion compound generated during nucleic acid amplification into potential, so as to achieve a real-time detection. The results can be transmitted to a smartphone via Bluetooth. Moreover, HIROF was applied in nucleic acid device detection, with a super-Nernst sensitivity of 77.6 mV/pH in the pH range of 6.0-8.5, and the sensitivity showed the best results so far. Detection of V. parahaemolyticus by this novel method showed a detection limit of 1.0 × 10 3  CFU/mL, while the time consumption was only 30 min, outperforming real-time fluorescence loop-mediated isothermal amplification (LAMP). Therefore, the characteristics of compact, portable, and fast make the sensor more widely used in on-site detection., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In the present report, a novel dual pH-O 2 sensor based on covalent conjugate of rhodamine 6G and cyclometalated iridium complex with poly(vinylpyrrolidone-block-vinyltetrazole) copolymer is reported. In model physiological solutions the sensor chromophores display independent phosphorescent and fluorescent lifetime responses onto variations in oxygen concentration and pH, respectively. Colocalization studies on Chinese hamster ovary cells demonstrate the preferential localization in endosomes and lysosomes. The fluorescent lifetime imaging microscopy-phosphorescent lifetime imaging microscopy (FLIM-PLIM) experiments show that the phosphorescent O 2 sensor provides unambiguous information onto hypoxia versus normoxia cell status as well as semi-quantitative data on the oxygen concentration in cells in between these two states. However, the results of FLIM measurements indicate that dynamic lifetime interval of the sensor (≈0.5 ns between pH values 5.0 and 8.0) is insufficient even for qualitative estimation of pH in living cells because half-width of lifetime distribution in the studied samples is higher than the sensor dynamic interval. Nevertheless, the variations in rhodamine emission intensity are much higher and allow rough discrimination of acidic and neutral cell conditions. Thus, the results of this study indicate that the suggested approach to the design of dual pH-O 2 sensors makes possible to prepare the biocompatible and water-soluble conjugate with fast cellular uptake., (© 2024 Wiley‐VCH GmbH.)

In this paper, three new iridium(III) complexes: [Ir(piq) 2 (DFIPP)]PF 6 (piq = deprotonated 1-phenylisoquinoline, DFIPP = 3,4-difluoro-2-(1 H -imidazo[4,5- f ][1,10]phenenthrolin-2-yl)phenol, 3a ), [Ir(bzq) 2 (DFIPP)]PF 6 (bzq = deprotonated benzo[ h ]quinoline, 3b ), and [Ir(ppy) 2 (DFIPP)]PF 6 (ppy = deprotonated 1-phenylpyridine, 3c ), were synthesized and characterized. The complexes were found to be nontoxic to tumor cells via 3-(4,5-dimethylthiazole-2-yl)-diphenyltetrazolium bromide (MTT) assay. Surprisingly, its liposome-entrapped complexes 3alip, 3blip, and 3clip on B16 cells showed strong cytotoxicity (IC 50 = 13.6 ± 2.8, 9.6 ± 1.1, and 18.9 ± 2.1 μM). Entry of 3alip, 3blip, and 3clip into B16 cells decreases mitochondrial membrane potential, regulates Bcl-2 family proteins, releases cytochrome c, triggers caspase family cascade reaction, and induces apoptosis. In addition, we also found that 3alip, 3blip, and 3clip triggered ferroptosis and autophagy. In vivo studies demonstrated that 3blip inhibited melanoma growth in C57 mice with a high inhibitory rate of 83.95%, and no organic damage was found in C57 mice.

Triggering ferroptosis represents a promising anticancer therapeutic strategy, but the development of a selective ferroptosis inducer for cancer-specific therapy remains a great challenge. Herein, a H 2 S-responsive iridium(III) complex NA-Ir has been well-designed as a ferroptosis inducer. NA-Ir could selectively light up H 2 S-rich cancer cells, primarily localize in mitochondria, intercalate into mitochondrial DNA (mtDNA), and induce mtDNA damage, exhibiting higher anticancer activity under light irradiation. Mechanistic studies showed that NA-Ir -mediated PDT triggered lipid peroxidation and glutathione peroxidase 4 downregulation through ROS production and GSH depletion, resulting in ferroptosis through multiple pathways. Moreover, the intense mtDNA damage can activate the cyclic GMP-AMP synthase-stimulator of the interferon gene (cGAS-STING) pathway, leading to ferritinophagy and further ferroptosis. RNA-sequencing analysis showed that NA-Ir -mediated PDT mainly affects the expression of genes related to ferroptosis, autophagy, and cancer immunity. This study demonstrates the first cancer-specific example with ferroptosis and cGAS-STING activation, which provides a new strategy for multimodal synergistic therapy.

Photodynamic therapy delivers more targeted cell killing than classical chemotherapy. It uses light-absorbing compounds, photosensitizers (PSs), to generate lethal reactive oxygen species (ROS) at sites of localized irradiation. Transition metal complexes are attractive PSs due to their photostability, visible-light absorption, and high ROS yields. Here, we introduce a low-molecular weight, photostable iridium complex, [Ir(thpy) 2 (benz)]Cl, 1 , that localizes to the Golgi apparatus, mitochondria, and endoplasmic reticulum, absorbs visible light, phosphoresces strongly, generates 1 O 2 with 43% yield, and undergoes cellular elimination after 24 h. 1 shows low dark toxicity and under remarkably low doses (3 min, 20-30 mJ s -1 cm -2 ) of 405 or 455 nm light, it causes killing of bladder (EJ), malignant melanoma (A375), and oropharyngeal (OPSCC72) cancer cells, with high phototoxic indices > 100-378. 1 is also an efficient PS in 3D melanoma spheroids, with repeated short-time irradiation causing cumulative killing.

Cross-linking strategies have found wide applications in chemical biology, enabling the labeling of biomolecules and monitoring of protein-protein interactions. Nitrone exhibits remarkable versatility and applicability in bioorthogonal labeling due to its high reactivity with strained alkynes via the strain-promoted alkyne-nitrone cycloaddition (SPANC) reaction. In this work, four cyclometalated iridium(III) polypyridine complexes functionalized with two nitrone units were designed as novel phosphorogenic bioorthogonal reagents for bioimaging and phototherapeutics. The complexes showed efficient emission quenching, which is attributed to an efficient nonradiative decay pathway via the low-lying T 1 /S 0 minimum energy crossing point (MECP), as revealed by computational studies. However, the complexes displayed significant emission enhancement and lifetime extension upon reaction with (1 R ,8 S ,9 s )-bicyclo[6.1.0]non-4-yne (BCN) derivatives. In particular, they showed a remarkably higher reaction rate toward a bis -cyclooctyne derivative ( bis -BCN) compared with its monomeric counterpart ( mono -BCN). Live-cell imaging and (photo)cytotoxicity studies revealed higher photocytotoxicity in bis -BCN-pretreated cells, which is ascribed to the enhanced singlet oxygen ( 1 O 2 ) photosensitization resulting from the elimination of the nitrone-associated quenching pathway. Importantly, the cross-linking properties and enhanced reactivity of the complexes make them highly promising candidates for the development of hydrogels and stapled/cyclized peptides, offering intriguing photophysical, photochemical, and biological properties. Notably, a nanosized hydrogel ( 2-gel ) demonstrated potential as a drug delivery system, while a stapled peptide ( 2- bis -pDIKK ) exhibited p53-Mdm2 inhibitory activity related to apoptosis and a cyclized peptide ( 2- bis -RGD ) showed cancer selectivity.

Cyclometalated iridium(III) compounds have been widely explored due to their outstanding photo-physical properties and multiple anticancer activities. In this paper, three cyclometalated iridium(III) compounds [Ir(ppy) 2 (DBDIP)]PF 6 (5a), [Ir(bzq) 2 (DBDIP)]PF 6 (5b), and [Ir(piq) 2 (DBDIP)]PF 6 (5c) (ppy: 2-phenylpyridine; bzq: benzo[ h ]quinoline; piq: 1-phenylisoquinoline, and DBDIP: 2-(2,3-dihydrobenzo[ b ][1,4]dioxin-6-yl)-1 H -imidazo[4,5- f ][1,10]phenanthroline) were synthesized and the mechanism of antitumor activity was investigated. Compounds photoactivated by visible light show strong cytotoxicity against tumor cells, especially toward A549 cells. Biological experiments such as migration, cellular localization, mitochondrial membrane potential and permeability, reactive oxygen species (ROS) and calcium ion level detection were performed, and they demonstrated that the compounds induced the apoptosis of A549 cells through a mitochondrial pathway. At the same time, oxidative stress caused by ROS production increases the release of damage-related molecules and the expression of porogen gasdermin D (GSDMD), and the content of LDH released from damaged cell membranes also increased. Besides, the content of the lipid peroxidation product, malondialdehyde (MDA), increased and the expression of GPX4 decreased. These indicate that the compounds promote cell death by combining ferroptosis and pyroptosis. The results reveal that cyclometalated iridium(III) compounds 5a-5c may be a potential chemotherapeutic agent for photodynamic therapy of cancers.

Given the extensive role of lipids in cancer development, there is substantial clinical interest in developing therapies that target lipid metabolism. In this study, we identified one cyclometalated iridium complex ( Ir2 ) that exhibits potent antiproliferation activity in MIA PaCa-2 cells by regulating fatty acid metabolism and sphingolipid metabolism simultaneously. Ir2 also efficiently overcomes cisplatin resistance in vitro . Satisfyingly, the generated Ir2@F127 carriers, as a temperature-sensitiv e in situ gelling system of Ir2 , showed effective cancer treatment with minimal side effects in an in vivo xenograft study. To the best of our knowledge, Ir2 is the first reported cyclometalated iridium complex that exerts anticancer activity in MIA PaCa-2 cells by intervening in lipid metabolism, which provides an alternative pathway for the anticancer mechanism of cyclometalated iridium complexes.

A long-wavelength triggered cationic iridium(III) complex, Ir5, and its corresponding nanoparticles with the ability to generate type I and type II reactive oxygen species have been synthesised. The complex targets mitochondria and achieves an excellent photodynamic therapy effect in hypoxic cancer cells.

Herein, a novel sandwich electrochemiluminescence (ECL) aptasensor was developed based on the resonance energy transfer (RET) with iridium complex doped silicate nanoparticles (SiO 2 @Ir) as energy donor and gold nanoparticles modified TiVC MXene (AuNPs@TiVC) as energy acceptor. Strong anodic ECL signal of SiO 2 @Ir was obtained through both co-reactant pathway and annihilation pathway. Electrochemical results showed that SiO 2 @Ir has good electron transfer rate and large specific surface area to immobilize more aptamers. AuNPs@TiVC apparently quenched the ECL signal of SiO 2 @Ir due to the ECL resonance energy transfer between them. In the presence of kanamycin (KAN), a sandwich type sensor was formed with the aptamer probes as connecters between the donor and the acceptor, resulting in the decrease of ECL intensity. Under the optimal condition, KAN could be sensitively detected in the range of 0.1 pg/mL to 10 ng/mL with a low detection limit of 24.5 fg/mL. The proposed ECL system exhibited satisfactory analytical performance, which can realize the detection of various biological molecules by adopting suitable aptamer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In previous work, we reported on iridium(III) (Ir(III)) complex-peptide hybrids as amphiphilic conjugates (IPH-ACs) and triptycene-peptide hybrids as amphiphilic conjugates (TPH-ACs) and found that these hybrid compounds containing three cationic KK(K)GG peptide units through C 6 -C 8 alkyl linkers induce paraptosis II, which is one of the nonapoptotic programmed cell death (PCD) types in Jurkat cells and different from previously reported paraptosis. The details of that study revealed that the paraptosis II induced by IPH-ACs (and TPH-ACs) proceeds via a membrane fusion or tethering of the endoplasmic reticulum (ER) and mitochondria, and Ca 2+ transfer from the ER to mitochondria, which results in a loss of mitochondrial membrane potential ( ΔΨ m ) in Jurkat cells. However, the detailed mechanistic studies of paraptosis II have been conducted only in Jurkat cells. In the present work, we decided to conduct mechanistic studies of paraptosis II in HeLa-S3 and A549 cells as well as in Jurkat cells to study the general mechanism of paraptosis II. Simultaneously, we designed and synthesized new TPH-ACs functionalized with peptides that contain cyclohexylalanine, which had been reported to enhance the localization of peptides to mitochondria. We found that TPH-ACs containing cyclohexylalanine promote paraptosis II processes in Jurkat, HeLa-S3 and A549 cells. The results of the experiments using fluorescence Ca 2+ probes in mitochondria and cytosol, fluorescence staining agents of mitochondria and the ER, and inhibitors of paraptosis II suggest that TPH-ACs induce Ca 2+ increase in mitochondria and the membrane fusion between the ER and mitochondria almost simultaneously, suggesting that our previous hypothesis on the mechanism of paraptosis II should be revised.

The limited optical penetration depth and hypoxic tumor microenvironment (TME) are key factors that hinder the practical applications of conventional photodynamic therapy (PDT). To fundamentally address these issues, self-luminescent photosensitizers (PSs) can achieve efficient PDT. Herein, a self-chemiluminescence (CL)-triggered Ir complex PS, namely, IrL2 , with low-O 2 -dependence type I photochemical processes is reported for efficient PDT. The rational design achieves efficient chemiluminescence resonance energy transfer (CRET) from covalently bonded luminol units to the Ir complex in IrL2 under the catalysis of H 2 O 2 and hemoglobin (Hb) to generate O 2 •- and 1 O 2 . Liposome IrL2H nanoparticles (NPs) are constructed by loading IrL2 and Hb. The intracellular H 2 O 2 and loaded Hb catalyze the luminol part of IrL2H , and the Ir2 part is then excited to produce types I and II reactive oxygen species (ROS) through CRET, inducing cell death, even under hypoxic conditions, and promoting cell apoptosis. IrL2H is used for tumor imaging and inhibits tumor growth in 4T1-bearing mouse models through intratumoral injection without external light sources. This work provides new designs for transition metal complex PSs that conquer the limitations of external light sources and the hypoxic TME in PDT.

A series of biotin-functionalized transition metal complexes was prepared by iClick reaction from the corresponding azido complexes with a novel alkyne-functionalized biotin derivative ([Au(triazolato R,R' )(PPh 3 )], [Pt(dpb)(triazolato R,R' )], [Pt(triazolato R,R' )(terpy)]PF 6 , and [Ir(ppy)(triazolato R,R' )(terpy)]PF 6 with dpb = 1,3-di(2-pyridyl)benzene, ppy = 2-phenylpyridine, and terpy = 2,2':6',2''-terpyridine and R = C 6 H 5 , R' = biotin). The complexes were compared to reference compounds lacking the biotin moiety. The binding affinity toward avidin and streptavidin was evaluated with the HABA assay as well as isothermal titration calorimetry (ITC). All compounds exhibit the same binding stoichiometry of complex-to-avidin of 4:1, but the ITC results show that the octahedral Ir(III) compound exhibits a higher binding affinity than the square-planar Pt(II) complex. The antibacterial activity of the compounds was evaluated on a series of Gram-negative and Gram-positive bacterial strains. In particular, the neutral Au(I) and Pt(II) complexes showed significant antibacterial activity against Staphylococcus aureus and Enterococcus faecium at very low micromolar concentrations. The cytotoxicity against a range of eukaryotic cell lines was studied and revealed that the octahedral Ir(III) complex was non-toxic, while the square-planar Pt(II) and linear Au(I) complexes displayed non-selective micromolar activity., (© 2024. The Author(s), under exclusive licence to Society for Biological Inorganic Chemistry (SBIC).)

3-Methylhistidine (3-MeHis) is increasingly used as an indicator of muscle protein breakdown. The development of a sensitive, simple, and non-invasive method for 3-MeHis assay is important in clinical practice. Herein, a sensitive, simple, and non-invasive electrogenerated chemiluminescence (ECL) method was proposed for the quantitation of 3-MeHis in urine by using an iridium(III) solvent complex ([Ir(dfppy) 2 (DMSO)Cl], dfppy = 2-(2,4-difluorophenyl)pyridine, Ir-DMSO) as a signal reagent. The photoluminescence (PL) and ECL responses of Ir-DMSO to 3-MeHis were studied. The ECL intensity of Ir-DMSO was enhanced in the presence of 3-MeHis because of the coordination recognition between Ir-DMSO and the imidazole group of 3-MeHis. Based on the enhancement of ECL intensity, 3-MeHis can be sensitively detected in the range of 5 to 25 μM. The detection limit was 0.4 μM. This is the first report of an ECL method for the quantitation of 3-MeHis. Further, to investigate the feasibility of the Ir-DMSO-based ECL method in practical applications, the developed ECL method was applied for 3-MeHis assay in urine samples of 28 healthy volunteers and 2 patients. The urine samples from patients hospitalized with obesity and kidney disease and healthy individuals were distinguished by the ECL responses of Ir-DMSO. The proposed ECL method based on the coordination recognition between iridium(III) solvent complex and the imidazole group of 3-MeHis allows inexpensive, fast, non-invasive, and sensitive detection of 3-MeHis in urine, which is promising for assessing large volumes of patients for routine analysis in clinical practices., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Bisphenol S (BPS) is a common pollutant in the environment and has posed a potential threat to aquatic animals and human health. To accurately assess the pollution level and ecological risk of BPS, there is an urgent need to establish simple and sensitive detection methods for BPS. In this study, BPS complete antigen was successfully prepared by introducing methyl 4-bromobutyrate and coupling bovine serum albumin (BSA). The monoclonal antibody against BPS (anti-BPS mAb) with high affinity (1: 256,000) was developed based on the BPS complete antigen, which showed low cross-reactivity with BPS structural analogues. Then, an electrochemical immunosensor was constructed to detect BPS using multi-walled carbon nanotubes and gold nanoflower composites as signal amplification elements and using anti-BPS mAb as the probe. The electrochemical immunosensor had a linear range from 1 to 250 ng⋅mL -1 and a limit of detection (LOD) down to 0.6 ng⋅mL -1 . Additionally, a more stable and sensitive lateral flow immunoassay (LFIA) for BPS was developed based on iridium oxide nanoparticles, with a visual detection limit of 1 ng⋅mL -1 , which was 10 times lower than that of classical Au-NPs LFIA. After evaluation of their stability and specificity, the reliability of these two methods were further validated by measuring BPS concentrations in the water and fish tissues. Thus, this study provides sensitive, robust and rapid methods for the detection of BPS in the environment and organisms, which can provide a methodological reference for monitoring environmental contaminants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Dinuclear iridium(III) complexes activated by light-inducible spatiotemporal control are emerging as promising candidates for cancer therapy. However, broader applications of current light-activated dinuclear iridium(III) complexes are limited by the ineffective tissue penetration and undesirable feedback on guidance activation. Here, an ultrasound (US) triggered near infrared-fluorescent dinuclear iridium(III) nanoparticle, NanoIr, is first reported to precisely and spatiotemporally inhibit tumor growth. It is demonstrated that reactive oxygen species can be generated by NanoIr upon exposure to US irradiation (NanoIr + US), thereby inducing immunogenic cell death. When combined with cisplatin, NanoIr + US elicits synergistic effects in patient-derived tumor xenograft mice models of ovarian cancer. This work first provides a design of dinuclear iridium(III) nanoparticles for immunogenic sonodynamic therapy., (© 2024 Wiley‐VCH GmbH.)

A diverse set of neutral half-sandwich iminoamido iridium and ruthenium organometallic complexes is synthesized through the utilization of Schiff base pro-ligands with N ˄ N donors. Notably, these metal complexes with varying leaving groups (Cl - or OAc - ) are formed by employing different quantities of the deprotonating agent NaOAc, and exhibit promising cytotoxicity against various cancer cell lines such as A549 and cisplatin-resistant A549/DDP lung cancer cells, as well as HeLa cells, with IC 50 values spanning from 9.26 to 15.98 μM. Cytotoxicity and anticancer selectivity (SI: 1.9-2.4) of these metal complexes remain unaffected by variations in the metal center, leaving group, and ligand substitution. Further investigations reveal that these metal complexes specifically target mitochondria, leading to the depolarization of the mitochondrial membrane and instigating the production of intracellular reactive oxygen species. Furthermore, the metal complexes are found to induce late apoptosis and disrupt the cell cycle, leading to G 2 /M cell cycle arrest specifically in A549 cancer cells. In light of these findings, it is evident that the primary mechanism contributing to the anticancer effectiveness of these metal complexes is the redox pathway., Competing Interests: Declaration of competing interest The authors declare the following potential competing interests: Some of the compounds in this paper are protected under patent CN116731080A (in the substantive examination stage), issued on September 12, 2023. The patent holders are some of the authors of this paper., (Copyright © 2023. Published by Elsevier Inc.)

Over the last decades, a variety of metal complexes have been developed as chemotherapeutic agents. Despite the promising therapeutic prospects, the vast majority of these compounds suffer from low solubility, poor pharmacological properties, and most importantly poor tumor accumulation. To circumvent these limitations, herein, the incorporation of cytotoxic Ir(III) complexes and a variety of photosensitizers into polymeric gemini nanoparticles that selectively accumulate in the tumorous tissue and could be activated by near-infrared (NIR) light to exert an anticancer effect is reported. Upon exposure to light, the photosensitizer is able to generate singlet oxygen, triggering the rapid dissociation of the nanostructure and the activation of the Ir prodrug, thereby initiating a cascade of mitochondrial targeting and damage that ultimately leads to cell apoptosis. While selectively accumulating into tumorous tissue, the nanoparticles achieve almost complete eradication of the cisplatin-resistant cervical carcinoma tumor in vivo upon exposure to NIR irradiation., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

As a vital factor in cell metabolism, nitric oxide (NO) is associated with nitrosative stress and subsequent inflammations and diseases. In situ, real-time NO monitoring is challenging due to its relative trace concentration and fast diffusion in cell. Scanning electrochemical microscopy (SECM) is suited uniquely for single-cell analysis, and its electrochemical response to targets can be further enhanced by improving the interfacial properties of its tip. Here, an ultramicroelectrodes (UMEs) modification strategy based on bimetallic single-particle was proposed for the first time. This mesoporous platinum/iridium alloy single-particle (mPtIr SP) interface using micelle-assisted electrodeposition was characterized by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). And the nucleation kinetic progress which can be defined as "oil-in-water-like" electrodeposition was discussed in detail. The high sensitivity (203.86 μA/μM·cm 2 ) and good selectivity for NO detection benefits from the high catalysis of the PtIr alloy and the high mass transfer properties of the porous interface. In particular, this novel UME can real-time monitor NO release from a single MCF-7 cell stimulated by perfluorooctanoic acid (PFOA), providing new ideas for contaminant toxicity assessment, health diagnostics, and disease treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Transition metal-coordinated porphyrin metal-organic frameworks (MOFs) were perspective in photodynamic therapy (PDT) and catalytic therapy. However, the tumor hypoxia and the insufficient endogenous hydrogen peroxide (H 2 O 2 ) seriously limited their efficacies. Herein, by encapsulating ultrasmall iridium (Ir) and modifying glucose oxidase (GOx), an iron-coordinated porphyrin MOF (Fe-MOF) nanoplatform (Fe-MOF@Ir/GOx) was designed to strengthen PDT/catalytic therapy by producing reactive oxygen species (ROS) storm. In this nanoplatform, Fe-MOF showed glutathione (GSH)-responsive degradation, by which porphyrin, GOx and ultrasmall Ir were released. Moreover, ultrasmall Ir possessed dual-activities of catalase (CAT)-like and peroxidase (POD)-like, which provided sufficient oxygen (O 2 ) to enhance PDT efficacy, and hydroxyl radical (·OH) production was also improved by combining Fenton reaction of Fe 2+ . Further, GOx catalyzed endogenous glucose produced H 2 O 2 , also reduced pH value, which accelerated Fenton reaction and resulted in generation of ROS storm. Therefore, the developed Fe-MOF@Ir/GOx nanoplatform demonstrated enhanced PDT/catalytic therapy by producing ROS storm, and also provided a promising strategy to promote degradation/metabolism of inorganic nanoplatforms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cortisol is a well-known stress biomarker; this study focuses on using electrochemical immuno-sensing to measure the concentration of cortisol selectively and sensitively in artificial samples. Anti-cortisol antibodies have been immobilised on polycrystalline Au electrodes via strong covalent thiol bonds, fabricating an electrochemical bio-immunosensor for cortisol detection. IrO x was then anodically electrodeposited as a reference electrode on a commercial screen-printed electrode and electrochemical impedance spectrometry (EIS) studies were used to correlate the electrochemical response to cortisol concentration and the induced changes in charge transfer resistance (R ct ). A linear relationship between the R ct and the logarithm of cortisol concentration was found in concentrations ranging from 1 ng/mL to 1 mg/mL with limit of detection at 11.85 pg/mL (32.69 pM). The modification of the reference electrode with iridium oxide has greatly improved the reproducibility of the screen-printed electrode. The sensing system can provide a reliable and sensitive detection approach for cortisol measurements., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

In this study, the ligand EIPP (5-ethoxy-2-(1H-imidazo[4,5-f] [1,10] phenanthrolin-2-yl)phenol) and [Ir(ppy) 2 (EIPP)](PF 6 )] (5a, ppy = 2-phenylpyridine) and [Ir(piq) 2 (EIPP)](PF 6 )] (5b, piq = 1-phenylisoquinoline) were synthesized and they were entrapped into liposomes to produce 5alipo and 5blipo. 5a and 5b were characterized via HRMS, NMR, UV-vis and IR. The cytotoxicity of 5a, 5b, 5alipo and 5blipo on cancer and non-cancer cells was estimated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). MTT assay demonstrated that 5a and 5b did not show any significant cellular activity but their liposome-encapsulated 5alipo and 5blipo had significant toxic effects. The mechanism of 5alipo, 5blipo-inducing apoptosis was explored by studying cellular uptake, mitochondrial localization, mitochondrial membrane potential, cytochrome C, glutathione (GSH), malondialdehyde (MDA) and protein immunoblotting. The results demonstrated that 5alipo and 5blipo caused a release of cytochrome C, downregulated the expression of Bcl-2, upregulated the expression of BAX, activated caspase 3, and downregulated PARP expression. It was shown that 5alipo and 5blipo could inhibit cancer cell proliferation in G2/M phase by regulating p53 and p21 proteins. Additionally, 5alipo and 5blipo induced autophagy through an adjustment from LC3-I to LC3-II and caused ferroptosis. The in vivo antitumor activity of 5alipo was examined in detail., Competing Interests: Declaration of competing interest The authors declare no competing interest exists., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Temperature has a profound influence on various neuromodulation processes and has emerged as a focal point. However, the effects of acute environmental temperature fluctuations on cultured cortical networks have been inadequately elucidated. To bridge this gap, we have developed a brain-on-a-chip platform integrating cortical networks and electrodeposited Pt/Ir modified microelectrode arrays (MEAs) with 3D-printed bear-shaped triple chambers, facilitating control of temperature transients. This innovative system administers thermal stimuli while concurrently monitoring neuronal activity, including spikes and local field potentials, from 60 microelectrodes (diameter: 30 μm; impedance: 9.34 ± 1.37 kΩ; and phase delay: -45.26 ± 2.85°). Temperature transitions of approximately ±10 °C/s were applied to cortical networks on MEAs via in situ perfusion within the triple chambers. Subsequently, we examined the spatiotemporal dynamics of the brain-on-a-chip under temperature regulation at both the group level (neuronal population) and their interactions (network dynamics) and the individual level (cellular activity). Specifically, we found that after the temperature reduction neurons enhanced the overall information transmission efficiency of the network through synchronous firing to compensate for the decreased efficiency of single-cell level information transmission, in contrast to temperature elevation. By leveraging the integration of high-performance MEAs with perfusion chambers, this investigation provides a comprehensive understanding of the impact of temperature on the spatiotemporal dynamics of neural networks, thereby facilitating future exploration of the intricate interplay between temperature and brain function.

The aggregation of amyloid β (Aβ) peptides is a significant hallmark of Alzheimer's disease (AD), and the detection of Aβ aggregates and the inhibition of their formation are important for the diagnosis and treatment of AD, respectively. Herein, we report a series of benzothiazole-based Ir(III) complexes HN-1 to HN-8 that exhibit appreciable inhibition of Aβ aggregation in vitro and in living cells. These Ir(III) complexes can induce a significant fluorescence increase when binding to Aβ fibrils and Aβ oligomers, while their measured log  D values suggest these compounds could have enhanced blood-brain barrier (BBB) permeability. In vivo studies show that HN-1, HN-2, HN-3, and HN-8 successfully penetrate the BBB and stain the amyloid plaques in AD mouse brains after a 10-day treatment, suggesting that these Ir(III) complexes could act as lead compounds for AD therapeutic and diagnostic agent development.

In this paper, we present the synthesis of four new complexes: the dimeric precursor [Ir(dmppz) 2 ( μ -Cl)] 2 (1) (Hdmppz - 3,5-dimethyl-1-phenyl-1 H -pyrazole) and heteroleptic bis-cyclometalated complexes: [Ir(dmppz) 2 (Py 2 CO)]PF 6 ·½CH 2 Cl 2 (2), [Ir(dmppz) 2 (H 2 biim)]PF 6 ·H 2 O (3), and [Ir(dmppz) 2 (PyBIm)]PF 6 (4), with auxiliary N,N-donor ligands: 2-di(pyridyl)ketone (Py 2 CO), 2,2'-biimidazole (H 2 biim) and 2-(2'-pyridyl)benzimidazole (PyBIm). In the obtained complexes, SC-X-ray analysis revealed that Ir(III) has an octahedral coordination sphere with chromophores of the type {IrN 2 C 2 Cl 2 } (1) or {IrN 4 C 2 } (2-4). The complexes obtained, which have been fully characterised by physicochemical methods (CHN, TG, FTIR, UV-Vis, PL and 1 H, 13 C, 15 N NMR), were used to continue our studies on the factors influencing the cytotoxic properties of potential chemotherapeutic agents ( in vitro ). To this end, the following studies are presented: (i) comparative analysis of the effects on the biological properties of N,N-donor ligands and C,N-donor ligands in the studied complexes, (ii) studies of the interactions of the compounds with the selected molecular target: DNA and BSA (UV-Vis, CD and PL methods), (iii) and the reactivity towards redox molecules: GSH, NADH (UV-Vis and/or ESI-MS methods), (iv) cytotoxic activity (IC 50 ) of potential chemotherapeutics against MCF-7, K-562 and CCRF-CEM cell lines.

Background: The six Platinum group metal elements (PGEs) comprising Ruthenium, Rhodium, Palladium, Platinum, Iridium and Osmium are grouped together in the periodic table. Human activities are mostly responsible for releasing PGEs into the environment. This systematic review focused on three PGEs with the greatest anthropogenic use, including in vehicle catalytic converters: Platinum (Pt), Palladium (Pd), and Rhodium (Rh). Consequently, these represent the greatest contributors to environmental pollution. The current review of in vivo toxicological studies (mammalian models) and in vitro cell exposure studies examined the potential harmful effects of these metalloids to mammalians, and their possible toxicity to human health., Methods: We applied Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology to conduct a comprehensive search and evaluation of records in the available literature published between 01/01/2009 and 01/15/2024 in four databases. PROSPERO code ID: CRD42024471558. Results concerning the health effects of PGEs were extracted from articles according to the inclusion and exclusion criteria. After screening the records for eligibility, 22 studies were included in the final analysis., Results: This systematic review revealed that airborne PGEs significantly increased the activation of pathologic pathways in several human organs and/or perturbed various metabolic pathways. In view of the known pro-inflammatory and organ-degenerative effects of PGEs, the paucity of studies on the effect of PGEs on the central nervous system and on possible correlations with neurodegenerative diseases were particularly evident., Conclusions: The clinical complexity and chronic nature of PGE-related pathologies indicate that targeted research is essential. In light of the increasing incidence of non-communicable diseases, particular attention should be paid to the design of epidemiological studies and to environmental monitoring services., Competing Interests: The authors declare that they have no conflict of interest. Gea Oliveri Conti is serving as one of the Editorial Board members of this journal. We declare that Gea Oliveri Conti had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Antoni Camins., (© 2024 The Author(s). Published by IMR Press.)

Iridium(III) complexes nowadays became rising stars in various health-related applications. Thus, there is a necessity to assess cytotoxicity of the synthesized molecules against cancer/normal cell lines. In this report, we present a dataset of 2694 experimental cytotoxicity values of 803 iridium complexes against 127 different cell lines. We specify the experimental conditions and provide representation of the complexes molecules in machine-readable format. The dataset provides a starting point for exploration of new iridium-based cellular probes and opens new possibilities for predictions of toxicities and data-driven generation of new organometallic anticancer agents., (© 2024. The Author(s).)