Ruthenium(ii)-Arene Complex Triggers Immunogenic Ferroptosis for Reversing Drug Resistance.

Chemoresistance remains an arduous challenge in oncology, but ferroptosis shows potential for overcoming it by stimulating the immune system. Herein, a novel high-performance ruthenium(II)-based arene complex [Ru(η--cym)(BTBpy)Cl] () is developed for ferroptosis-enhanced antitumor immunity and drug resistance reversal via glutathione (GSH) metabolism imbalance. shows significantly enhanced antiproliferation activity against cisplatin (CDDP)-resistant lung cancer cells (A549R), with 26.

Molecular probes for super-resolution imaging of drug dynamics.

Super-resolution molecular probes (SRMPs) are essential tools for visualizing drug dynamics within cells, transcending the resolution limits of conventional microscopy. In this review, we provide an overview of the principles and design strategies of SRMPs, emphasizing their role in accurately tracking drug molecules. By illuminating the intricate processes of drug distribution, diffusion, uptake, and metabolism at a subcellular and molecular level, SRMPs offer crucial insights into therapeutic interventions.

Mitochondria-targeted ruthenium complexes can be generated in vitro and in living cells to target triple-negative breast cancer cells by autophagy inhibition.

Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer, which owned severe resistance to platinum-based anticancer agents. Herein, we report a new metal-arene complex, Ru-TPE-PPh, which can be synthesized in vitro and in living cells with copper catalyzed the cycloaddition reaction of Ru-azide and alkynyl (CuAAC). The complex Ru-TPE-PPh exhibited superior inhibition of the proliferation of TNBC MDA-MB-231 cells with an IC value of 4.

Cyclometalated iridium(III) complexes as anti-breast cancer and anti-metastasis agents via STAT3 inhibition.

Breast cancer is the most commonly diagnosed cancer and second‑leading cause of cancer deaths in women. Signal transducer and activator of transcription 3 (STAT3) plays a critical role in promoting breast cancer cell proliferation, invasion, angiogenesis, and metastasis, and the high expression of STAT3 is related to the occurrence and poor chemotherapy sensitivity of breast cancer. Iridium(III) complexes Ir-PTS-1- 4 containing a pterostilbene-derived ligand were synthesized to inhibit the STAT3 pathway in breast cancer.

Novel 1,8-Naphthalimide Derivatives As Antitumor Agents and Potent Demethylase Inhibitors.

Functional 1,8-naphthalimide derivatives are rapidly developing in the field of anticancer research. Herein, we designed and synthesized a series of naphthalimide derivatives with different substituents. Interestingly, 1,8-naphthalimide derivatives and inhibited a human demethylase FTO (the fat mass and obesity-associated protein).

Evoking Ferroptosis by Synergistic Enhancement of a Cyclopentadienyl Iridium-Betulin Immune Agonist.

Ferroptosis is a form of programmed cell death driven by iron-dependent lipid peroxidation (LPO) with the potential for antitumor immunity activation. In this study, a nonferrous cyclopentadienyl metal-based ferroptosis inducer [Ir(Cp*)(Bet)Cl]Cl (Ir-Bet) was developed by a metal-ligand synergistic enhancement (MLSE) strategy involving the reaction of [Ir(Cp*)Cl] Cl with the natural product Betulin. The fusion of Betulin with iridium cyclopentadienyl (Ir-Cp*) species as Ir-Bet not only tremendously enhanced the antiproliferative activity toward cancer cells, but also activated ferritinophagy for iron homeostasis regulation by PI3K/Akt/mTOR cascade inhibition with a lower dosage of Betulin, and then evoked an immune response by nuclear factor kappa-B (NF-κB) activation of Ir-Cp* species.

Selectively attacking tumor cells of Ru/Ir-arene complexes based on meclofenamic acid cyclooxygenase-2 inhibition.

Breast cancer (BC) is one of the most common malignant tumors and often accompanied by inflammatory processes. Inflammation is an essential component of the tumor microenvironment, which might influence tumor proliferation and metastasis. Herein, three metal-arene complexes MA-bip-Ru, MA-bpy-Ir, and MA-bpy-Ru were prepared by tethering the non-steroidal anti-inflammatory drug meclofenamic acid (MA).

Immunostimulation with chemotherapy of a ruthenium-arene complex via blockading CD47 signal in chronic myelogenous leukemia cells.

Combination of novel immunomodulation and traditional chemotherapy has become a new tendency in cancer treatment. Increasing evidence suggests that blocking the "don't eat me" signal transmitted by the CD47 can promote the phagocytic ability of macrophages to cancer cells, which might be promising for improved cancer chemoimmunotherapy. In this work, we conjugated CPI-alkyne modified by Devimistat (CPI-613) with ruthenium-arene azide precursor Ru-N by copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction to construct Ru complex CPI-Ru.

Self-Assembly Mitochondria-Targeting Donor-Acceptor Type Theranostic Nanosphere Activates ROS Storm for Multimodal Cancer Therapy.

The rational design of cancer theranostics with natural diagnostic information and therapeutic behavior has been considered to be a big challenge, since common theranostics from photothermal and photodynamic therapy need to be activated with external stimuli of photoirradiation to enable the chemotherapeutic effects. In this contribution, we have designed and synthesized a series of simple theranostic agents, ( = 4, 8, 12), which could accumulate at the tumor site over 48 h and indicate superior antiproliferative performance . was constructed with electron donor triphenylamine-acceptor benzothiadiazole-mitochondria-targeting moiety pyridinium.

Switching the Mode of Cell Death between Apoptosis and Autophagy by Histone Deacetylase 6 Inhibition Levels.

Inhibition of histone deacetylase (HDAC) has been demonstrated to be an effective strategy for cancer treatment. In this work, we have developed a new agent Ir-VPA, which exhibits the cell death mode switching between apoptosis and autophagy due to the distinct level of HDAC6 inhibition. Ir-VPA indicates the best anticancer activity to HeLa cells, and could be hydrolyzed due to the high expression of the esterase in HeLa cells.

Unlocking the potential of iridium and ruthenium arene complexes as anti-tumor and anti-metastasis chemotherapeutic agents.

It is a major challenge to design novel multifunctional metal-based chemotherapeutic agents for anti-tumor and anti-metastasis applications. Two complexes (OA-Ir and OA-Ru) were synthesized via CuAAC (copper-catalyzed azide-alkyne cycloaddition) reaction from nontoxic Ir-N or Ru-N species and low toxic alkynyl precursor OA-Alkyne, and exhibited satisfactory anti-tumor and anti-metastasis pharmacological effects. Conjugation of Oleanolic acid (OA) and metal-arene species significantly enhanced the cytotoxicity in A2780 cells compared to the precursors through mitochondrial-induced autophagy pathway.

The cyclometalated iridium (III) complex based on 9-Anthracenecarboxylic acid as a lysosomal-targeted anticancer agent.

9-Anthracenecarboxylic acid (9-Ac) was reported early as a chloride channel inhibitor and was found to exhibit significant anti-proliferative activity on leukemic cells, but has not been researched in solid tumor cells. Herein, a 9-anthraceneic acid derivative was introduced into the cyclometalated Iridium (III) species to construct a novel Iridium (Ir) complex Ir-9-Ac, [Ir(ppy)(9-Ac-L)]PF (ppy = 2-phenylpyridine, 9-Ac-L = N-((4'-methyl-[2,2'-bipyridin]-4-yl)methyl)anthracene-9-carboxamide), which could accumulated in lysosomes. Ir-9-Ac showed good cytotoxic activity against several tumor cell lines, notably on A549 cells.

A New Strategy to Fight Metallodrug Resistance: Mitochondria-Relevant Treatment through Mitophagy to Inhibit Metabolic Adaptations of Cancer Cells.

Metabolic adaptations can help cancer cells to escape from chemotherapeutics, mainly involving autophagy and ATP production. Herein, we report a new rhein-based cyclometalated Ir complex, Ir-Rhein, that can accurately target mitochondria and effectively inhibit metabolic adaptations. The complex Ir-Rhein induces severe mitochondrial damage and initiates mitophagy to reduce the number of mitochondria and subsequently inhibit both mitochondrial and glycolytic bioenergetics, which eventually leads to ATP starvation death.

Fighting metallodrug resistance through alteration of drug metabolism and blockage of autophagic flux by mitochondria-targeting AIEgens.

Metallodrug resistance has attracted a great deal of attention in cancer treatment. According to the cisplatin (cis-Pt) anticancer mechanism, a new strategy to overcome cis-Pt resistance through mitochondrial dysfunction is proposed. Two mitochondria-targeted aggregation-induced emission fluorogens (AIEgens) were first synthesized, named DP-PPh and TPE-PPh, which showed superior capacities to overcome the cis-Pt resistance of lung cancer cells (A549R) by the alteration of drug metabolism (up-regulation of influx CTR1 and down-regulation of efflux MRP2) and blockage of autophagic flux (failure of the degradation of autophagosomes).

Biotinylated curcumin as a novel chemosensitizer enhances naphthalimide-induced autophagic cell death in breast cancer cells.

Achieving selective release of chemical anticancer agents and improving therapeutic efficacy has always been a hot spot in the field of cancer research, yet how to achieve this remains a great challenge. In this work, we constructed a novel chemical anticancer agent (named MCLOP) by introducing naphthalimide into the skeleton of methylene blue (MB). Under the stimulation by cellular hypochlorous acid (HClO) and visible light, selective release of active naphthalimide can be achieved within breast cancer cell lines, the release process of which can be tracked visually using near-infrared fluorescence of MB (685 nm).

Mitochondria-targeted Pt(IV) prodrugs conjugated with an aggregation-induced emission luminogen against breast cancer cells by dual modulation of apoptosis and autophagy inhibition.

Theranostic anticancer agents with dual functions of diagnosis and therapy are in highly demand for breast cancer. Herein, a triphenylphosphonium (TPP)-decorated aggregation-induced emission (AIE)-based Pt(IV) prodrug ACPt was developed, which exhibited superior anticancer performance with novel anticancer mechanism of dual modulation of apoptosis and autophagy inhibition. The experimental data showed that ACPt induced increased reactive oxygen species (ROS), and decreased mitochondrial membrane potential (MMP).

Using bio-orthogonally catalyzed lethality strategy to generate mitochondria-targeting anti-tumor metallodrugs and .

Synthetic lethality was proposed nearly a century ago by geneticists and recently applied to develop precision anti-cancer therapies. To exploit the synthetic lethality concept in the design of chemical anti-cancer agents, we developed a bio-orthogonally catalyzed lethality (BCL) strategy to generate targeting anti-tumor metallodrugs both and Metallodrug Ru-rhein was generated from two non-toxic species Ru-N and rhein-alkyne via exclusive endogenous copper-catalyzed azide alkyne cycloaddition (CuAAC) reaction without the need of an external copper catalyst. The non-toxic species Ru-arene complex Ru-N and rhein-alkyne were designed to perform this strategy, and the mitochondrial targeting product Ru-rhein was generated in high yield (>83%) and showed high anti-tumor efficacy .

Photoactivated Osmium Arene Anticancer Complexes.

Half-sandwich Os-arene complexes exhibit promising anticancer activity, but their photochemistry has hardly been explored. To exploit the photocytotoxicity and photochemistry of Os-arenes, -chelated complexes [Os(η--cymene)(Curc)Cl] (, Curc = curcumin) and [Os(η-biphenyl)(Curc)Cl] (), and -chelated complexes [Os(η-biphenyl)(dpq)I]PF (, dpq = pyrazino[2,3-][1,10]phenanthroline) and [Os(η-biphenyl)(bpy)I]PF (, bpy = 2,2'-bipyridine), have been investigated. The Os-arene curcumin complexes showed remarkable photocytotoxicity toward a range of cancer cell lines (blue light IC: 2.

Monitoring hydrogen polysulfide during ferroptosis with a two-photon fluorescent probe.

Hydrogen polysulfide (HS, n > 1), a member of reactive sulfur species (RSS), is primarily generated during the crosstalk between HS and reactive oxygen species (ROS), which plays important role in physiological and pathological processes. Ferroptosis is a new non-classical mode of cell death, in which ROS-associated lipid peroxidation and iron-dependent accumulation are the main features. However, the biological effects of HS on ferroptosis and the detailed mechanisms of action remain poorly understood.

A self-immolated fluorogenic agent triggered by HS exhibiting potential anti-glioblastoma activity.

Glioblastoma is the most common and aggressive type of malignant brain tumor with poor survival and limited therapeutic options. Theranostic anticancer agents with dual functions of diagnosis and therapy are highly attractive. Self-immolation reaction is a promising approach for theranostic prodrugs triggered by the tumor microenvironment.

Hydrogen sulfide triggered molecular agent for imaging and cancer therapy.

We developed an activatable molecular reagent, PNF, triggered by intracellular H2S in the lysosome to release the therapeutic drug amonafide, which can escape from the lysosome into the nucleus to induce autophagy of cancer cells. PNF exhibits potent inhibitory activity against cisplatin-resistant tumor cell lines.

Brain Imaging of Amyloid-β Aggregates in Alzheimer's Disease with a Near-Infrared Fluorescent Probe.

Abnormal accumulation of amyloid-β (Aβ) has been determined to be a critical factor for the progression of Alzheimer's disease (AD), which has motivated the development of new chemical approaches for early sensing and imaging of these Aβ aggregates. Herein, we report a new near-infrared (NIR) fluorescent probe for the selective monitoring of Aβ aggregates . This novel fluorophore, named , was based on the curcumin scaffold and was designed by introducing an intramolecular rotation donor and a quinoline functional group.

A nitrogen-doped NiCo2S4/CoO hollow multi-layered heterostructure microsphere for efficient oxygen evolution in Zn-air batteries.

Exploring highly effective and low-cost non-noble metal-based electrocatalysts for oxygen evolution reaction (OER) is critical for renewable energy conversion and metal-air batteries. Herein, a novel and high-efficient OER catalyst was reported with nitrogen-doped oxide/sulfide heterostructures (named N-NiCo2S4/CoO microsphere). The N-NiCo2S4/CoO microsphere was synthesized by annealing NiCo-BTC MOF to a multi-layered hollow structure of NiCo2O4 microspheres, followed by the direct vulcanization in the presence of NH4HCO3, resulting in an oxide/sulfide heterojunction.

Coordination-Bond-Driven Dissolution-Recrystallization Structural Transformation with the Expansion of Cuprous Halide Aggregate.

Metal-organic frameworks (MOFs) with cuprous-halide-aggregates have shown superiority as organic LED (OLED) and semiconductor materials, while engineering MOF flexibility by involving the expansion of cuprous aggregates remains a great challenge. In this particular work, a dissolution-recrystallization structural transformation (DRST) with the dramatic growth of Cu-I aggregates, from 2D to 3D has been successfully realized. The unsaturated coordination nodes (2-positional nitrogen atoms) in have been demonstrated to be the driven force for DRST to via the formation of coordination bonds.