Theranostic Rhenium(I)-Based ER-Phagy Retardant Promotes Immunogenic Cell Death.

ER-phagy is a double-edged sword in the occurrence, development, and treatment of cancer; especially, its functions in immunotherapy are still unknown. In this work, we designed a theranostic Re complex () containing a BODIPY-derived ligand and a β-carboline ligand to target the endoplasmic reticulum (ER) and block ER-phagy at the late stages. Interestingly, as validated both in vitro and in vivo, ER-phagy blockage greatly enhances the capability of to induce immunogenic cell death (ICD).

Ruthenium(II) Lipid-Mimics Drive Lipid Phase Separation to Arouse Autophagy-Ferroptosis Cascade for Photoimmunotherapy.

Lipid-mediated phase separation is crucial for the formation of lipophilic spontaneous domain to regulate lipid metabolism and homeostasis, furtherly contributing to multiple cell death pathways. Herein, a series of Ru(II) lipid-mimics based on short chains or midchain lipids are developed. Among them, Ru-LipM with two dodecyl chains significantly induces natural lipid phase separation via hydrocarbon chain-melting phase transitions.

Quantitative Determination of Endoplasmic Reticulum Viscosity during Immunogenic Cell Death by a Theranostic Rhenium Complex.

The endoplasmic reticulum (ER) is an important targeting organelle for metal-based immunogenic cell death (ICD) inducers. Metal complexes can induce ER stress by causing protein misfolding, which can be reflected by alternations in microenvironmental parameters, including viscosity. We present here a theranostic Re(I) complex () that shows viscosity-dependent emission intensity and lifetime.

Identification of mitochondrial ATP synthase as the cellular target of Ru-polypyridyl--carboline complexes by affinity-based protein profiling.

Ruthenium polypyridyl complexes are promising anticancer candidates, while their cellular targets have rarely been identified, which limits their clinical application. Herein, we design a series of Ru(II) polypyridyl complexes containing bioactive β-carboline derivatives as ligands for anticancer evaluation, among which shows suitable lipophilicity, high aqueous solubility, relatively high anticancer activity and cancer cell selectivity. The subsequent utilization of a photo-clickable probe, , serves to validate the significance of ATP synthase as a crucial target for through photoaffinity-based protein profiling.

Activation of the cGAS-STING pathway by a mitochondrial DNA-targeted emissive rhodium(iii) metallointercalator.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon (STING) pathway is a key mediator of innate immunity involved in cancer development and treatment. The roles of mitochondrial DNA (mtDNA) in cancer immunotherapy have gradually emerged. Herein, we report a highly emissive rhodium(iii) complex (Rh-Mito) as the mtDNA intercalator.

The role of anti-HMGB1 antibody and anti-moesin antibody in ANCA-associated vasculitis.

Objective: The study aims to evaluate the role of anti-high mobility group box 1 (HMGB1) antibody and anti-moesin antibody in the diagnosis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and its possible relationship with the different clinical manifestations.

Methods: The study involved 60 AAV patients, 58 patients with autoimmune disease other than AAV and 50 healthy subjects. The serum levels of anti-HMGB1 and anti-moesin antibodies were determined by enzyme-linked immunosorbent assay (ELISA), and the second determination was made 3 months after treatment of AAV patients.

Metals and inorganic molecules in regulating protein and nucleic acid phase separation.

The realization that liquid-liquid phase separation (LLPS) underlies the formation of membraneless compartments in cells has motivated efforts to modulate the condensation process of biomolecules. Increasing evidence shows that metals and inorganic molecules abundantly distributed in cells play important roles in the regulation of biomolecular condensation. Herein, we briefly reviewed the background of biomacromolecular phase separation and summarized the recent research progress on the roles of metals and inorganic molecules in regulating protein and nucleic acid phase separation in vitro and in cells.

High-flow nasal cannula oxygen therapy is superior to conventional oxygen therapy in intensive care unit patients after extubation.

Background: Optimal oxygen supply is the cornerstone of the management of critically ill patients after extubation. High flow oxygen system is an alternative to standard oxygen therapy. This research explored the efficacy of high-flow nasal cannula (HFNC) oxygen therapy in patients after extubation in the intensive care unit (ICU).

Pt(IV)-Deferasirox Prodrug Combats DNA Damage Repair by Regulating RNA N-Methyladenosine Methylation.

DNA damage repair is considered to be an important mechanism of cisplatin resistance, and the roles of iron homeostasis in action mechanisms of cisplatin have not been studied yet. Herein, a Pt(IV) prodrug () integrating cisplatin and the clinical oral iron-chelating agent deferasirox () is found to be highly active toward cisplatin-insensitive triple-negative breast cancer cells both and . RNA-sequencing shows that can downregulate genes related to the double-strand break (DSB) damage pathway significantly.

Self-Amplifying Iridium(III) Photosensitizer for Ferroptosis-Mediated Immunotherapy Against Transferrin Receptor-Overexpressing Cancer.

Photoimmunotherapy is attractive for cancer treatment due to its spatial controllability and sustained responses. This work presents a ferrocene-containing Ir(III) photosensitizer (IrFc1) that can bind with transferrin and be transported into triple-negative breast cancer (TNBC) cells via a transferrin receptor-mediated pathway. When the ferrocene in IrFc1 is oxidized by reactive oxygen species, its capability to photosensitize both type I (electron transfer) and type II (energy transfer) pathways is activated through a self-amplifying process.

Ru(II)-modified TiO nanoparticles for hypoxia-adaptive photo-immunotherapy of oral squamous cell carcinoma.

The alternations in the hypoxic and immune microenvironment are closely related to the therapeutic effect and prognosis of oral squamous cell carcinoma (OSCC). Herein, a new nanocomposite, TiO@Ru@siRNA is constructed from a ruthenium-based photosensitizer (Ru) modified-TiO nanoparticles (NPs) loaded with siRNA of hypoxia-inducible factor-1α (HIF-1α). Under visible light irradiation, TiO@Ru@siRNA can elicit both Type I and Type II photodynamic effects, which causes lysosomal damage, HIF-1α gene silencing, and OSCC cell elimination efficiently.

Simultaneous Photoactivation of cGAS-STING Pathway and Pyroptosis by Platinum(II) Triphenylamine Complexes for Cancer Immunotherapy.

Activation of the cyclic GMP-AMP synthase-stimulator of the interferon gene (cGAS-STING) pathway is a potent anticancer immunotherapeutic strategy, and the induction of pyroptosis is a feasible way to stimulate the anticancer immune responses. Herein, two Pt complexes (Pt1 and Pt2) were designed as photoactivators of the cGAS-STING pathway. In response to light irradiation, Pt1 and Pt2 could damage mitochondrial/nuclear DNA and the nuclear envelope to activate the cGAS-STING pathway, and concurrently induce pyroptosis in cancer cells, which evoked an intense anticancer immune response in vitro and in vivo.

Real-time tracking of ER turnover during ERLAD by a rhenium complex via lifetime imaging.

Endoplasmic reticulum (ER) degradation by autophagy (ER-phagy) is a recently revealed selective autophagy pathway that plays important roles in organelle turnover and protein degradation, but the biological functions of ER-phagy are largely unknown. Here, we present an ER-targeting Re(I) tricarbonyl complex (Re-ERLAD) that can accumulate in the ER, induce ER-to-lysosome-associated degradation (ERLAD) upon visible light irradiation, and label ER buds and track their morphological alterations during ER-phagy. The emission of Re-ERLAD is sensitive to viscosity, which is a key parameter reflecting the amount of unfolded protein in the ER.

Photodegradation of carbonic anhydrase IX a binding-enhanced ruthenium-based photosensitizer.

Carbonic anhydrase IX (CAIX) is overexpressed in many cancer types. Herein, a CAIX targeting and binding-enhanced ruthenium-based photodegrader, Ru-dppz-CAi, is constructed by conjugating the photosensitizer with the inhibiting group a rotatable moiety. The binding of Ru-dppz-CAi and CAIX leads to significant enhancement in the emission and photosensitizing properties.

Rising Interest in the Development of Metal Complexes in Cancer Immunotherapy.

Metal complexes have shown great potential in cancer immunotherapy. This review briefly introduces the basic concepts and strategies of cancer immunotherapy and summarizes the recent discoveries on the immune effects of traditional platinum-based anticancer compounds. In addition, we also outline the latest research progresses on metal complexes for cancer immunotherapy focusing on platinum, ruthenium, iridium, rhenium and copper complexes.

The Effect of Shionone on Sepsis-Induced Acute Lung Injury by the ECM1/STAT5/NF-κB Pathway.

The purpose of the present study was to estimate the effect of shionone (SHI) on sepsis-induced acute lung injury (ALI). The cecal ligation and puncture (CLP) surgery was performed to induce sepsis in mice. Pulmonary hematoxylin and eosin staining, the wet/dry ratio, myeloperoxidase (MPO) activity, and the survival rate were detected.

A Nuclear-Targeted AIE Photosensitizer for Enzyme Inhibition and Photosensitization in Cancer Cell Ablation.

The nucleus is considered the ideal target for anti-tumor therapy because DNA and some enzymes in the nucleus are the main causes of cell canceration and malignant proliferation. However, nuclear target drugs with good biosafety and high efficiency in cancer treatment are rare. Herein, a nuclear-targeted material MeTPAE with aggregation-induced emission (AIE) characteristics was developed based on a triphenylamine structure skeleton.

Ferroptosis-Enhanced Cancer Immunity by a Ferrocene-Appended Iridium(III) Diphosphine Complex.

Ferroptosis is a programmed cell death pathway discovered in recent years, and ferroptosis-inducing agents have great potential as new antitumor candidates. Here, we report a Ir complex (Ir1) containing a ferrocene-modified diphosphine ligand that localizes in lysosomes. Under the acidic environments of lysosomes, Ir1 can effectively catalyze Fenton-like reaction, produce hydroxyl radicals, induce lipid peroxidation, down-regulate glutathione peroxidase 4, and result in ferroptosis.

Inhibition of Aβ peptide aggregation by ruthenium(II) polypyridyl complexes through copper chelation.

Alzheimer's disease (AD) is known as a complex multifactorial syndrome and both metal chelators and amyloid β peptide (Aβ) inhibitors show promise against AD. Herein, four small hybrid compounds have been designed and synthesized utilizing 8-hydroxyquinoline, pyridine or imidazole as chelators and benzimidazole as the recognition moiety for AD treatment. These conjugates can capture Cu from Aβ and become dimers upon Cu coordination and show high efficiency for both Cu elimination and Aβ assembly inhibition.

Induction and Monitoring of DNA Phase Separation in Living Cells by a Light-Switching Ruthenium Complex.

Phase separation of DNA is involved in chromatin packing for the regulation of gene transcription. Visualization and manipulation of DNA phase separation in living cells present great challenges. Herein, we present a Ru(II) complex () with high DNA binding affinity and DNA "light-switch" behavior that can induce and monitor DNA phase separation both and in living cells.

Redirecting Cisplatin and Doxorubicin to Mitochondria Affords Highly Effective Platinum Prodrug Against Triple Negative Breast Cancer.

A mitochondria targeting dual-action platinum prodrug exhibits high anticancer activity in triple negative breast cancer cells. The complex intervenes in several cellular processes including DNA damage, perturbation of mitochondrial bioenergetics and induction of necrosis to kill cancer cells.

A Continuous Add-On Probe Reveals the Nonlinear Enlargement of Mitochondria in Light-Activated Oncosis.

Oncosis, depending on DNA damage and mitochondrial swelling, is an important approach for treating cancer and other diseases. However, little is known about the behavior of mitochondria during oncosis, due to the lack of probes for in situ visual illumination of the mitochondrial membrane and mtDNA. Herein, a mitochondrial lipid and mtDNA dual-labeled probe, MitoMN, and a continuous add-on assay, are designed to image the dynamic process of mitochondria in conditions that are unobservable with current mitochondrial probes.