Photodecaging of a Mitochondria-Localized Iridium(III) Endoperoxide Complex for Two-Photon Photoactivated Therapy under Hypoxia.

Despite the clinical success of photodynamic therapy (PDT), the application of this medical technique is intrinsically limited by the low oxygen concentrations found in cancer tumors, hampering the production of therapeutically necessary singlet oxygen (O). To overcome this limitation, we report on a novel mitochondria-localized iridium(III) endoperoxide prodrug (), which, upon two-photon irradiation in NIR, synergistically releases a highly cytotoxic iridium(III) complex (), singlet oxygen, and an alkoxy radical. was found to be highly (photo-)toxic in hypoxic tumor cells and multicellular tumor spheroids (MCTS) in the nanomolar range.

Cycloruthenated Self-Assembly with Metabolic Inhibition to Efficiently Overcome Multidrug Resistance in Cancers.

The synthesis and the evaluation of the efficacy of a cycloruthenated complex, RuZ, is reported, to overcome multi-drug resistance (MDR) in cancer cells. RuZ can self-assemble into nanoaggregates in the cell culture medium, resulting in a high intracellular concentration of RuZ in MDR cancer cells. The self-assembly significantly decreases oxygen consumption and inhibits glycolysis, which decreases cellular adenosine triphosphate (ATP) levels.

A mitochondrion-targeted BODIPY-Ir(III) conjugate as a photoinduced ROS generator for the oxidative destruction of triple-negative breast cancer cells.

Photodynamic therapy (PDT) provides an alternative option to root out localized triple-negative breast cancer (TNBC) and has been experiencing a surge of research interest over recent years. In this study, we put forward a paradigm of designing novel transition metal-based PSs with the following characteristics: favorable cell-permeability, significant light-harvesting ability and prominent ROS yield. A novel BODIPY-Ir(III) conjugate has been designed as a photoinduced ROS (O, ˙OH and ˙O) generator.

Ruthenium(II) complexes coordinated to graphitic carbon nitride: Oxygen self-sufficient photosensitizers which produce multiple ROS for photodynamic therapy in hypoxia.

The photodynamic therapy (PDT) of cancer is limited by tumor hypoxia as PDT efficiency depends on O concentration. A novel oxygen self-sufficient photosensitizer (Ru-g-CN) was therefore designed and synthesized via a facile one-pot method in order to overcome tumor hypoxia-induced PDT resistance. The photosensitizer is based on [Ru(bpy)] coordinated to g-CN nanosheets by Ru-N bonding.

Mitochondria-Targeting and Reversible Near-Infrared Emissive Iridium(III) Probe for ONOO/GSH Redox Cycles Monitoring.

Peroxynitrite (ONOO) and glutathione (GSH), two unique reactive species, play an essential regulating role in the oxidation and antioxidation in the living body and are closely associated with various physiological and pathological processes, like cancer, cardiovascular disorders, diabetes, inflammation, Alzheimer's disease, and hepatotoxicity. Thus, it is crucial to study mitochondria ONOO/GSH redox cycles by an effective molecular tool. In this work, a mitochondria-targeting and redox-reversible near-infrared (NIR) phosphorescent iridium complex, , has been synthesized and used for the detection and imaging of a cellular redox state by visualizing endogenous ONOO/GSH content.

Ruthenium(II) complexes as bioorthogonal two-photon photosensitizers for tumour-specific photodynamic therapy against triple-negative breast cancer cells.

Herein, we developed the first Ru(ii) complex-based bioorthogonal two-photon photosensitizers. Through bioorthogonal labelling, they realize effective tumour-specific photodynamic therapy against triple-negative breast cancer cells.

Nano-assembly of ruthenium(II) photosensitizers for endogenous glutathione depletion and enhanced two-photon photodynamic therapy.

Photodynamic therapy (PDT) is a promising noninvasive cancer treatment. PDT in the clinic faces several hurdles due to the unique tumor environment, a feature of which is high levels of glutathione (GSH). An excess amount of GSH consumes reactive oxygen species (ROS) generated by photosensitizers (PSs), reducing PDT efficiency.

Rational design of a lysosome-targeting and near-infrared absorbing Ru(ii)-BODIPY conjugate for photodynamic therapy.

A Ru(ii)-BODIPY conjugate has been rationally designed and exhibits an intense absorption in the NIR region to boost lysosome-targeted PDT in vitro and in vivo. The advantages of Ru(ii) and BODIPY were successfully instilled into the conjugate to yield highly effective PDT efficacy against malignant melanoma A375 cells (PI = 3448) and A375 mice xenografts.

An ER-Targeting Iridium(III) Complex That Induces Immunogenic Cell Death in Non-Small-Cell Lung Cancer.

Immunogenic cell death (ICD) is a vital component of therapeutically induced anti-tumor immunity. An iridium(III) complex (Ir1), containing an N,N-bis(2-chloroethyl)-azane derivate, as an endoplasmic reticulum-localized ICD inducer for non-small cell lung cancer (NSCLC) is reported. The characteristic discharge of damage-associated molecular patterns (DAMPs), that is, cell surface exposure of calreticulin (CRT), extracellular exclusion of high mobility group box 1 (HMGB1), and ATP, were generated by Ir1 in A549 lung cancer cells, accompanied by an increase in endoplasmic reticulum stress and reactive oxygen species (ROS).

Supramolecular Assembly of An Organoplatinum(II) Complex with Ratiometric Dual Emission for Two-Photon Bioimaging.

The organoplatinum(II) complex [Pt(C^N^N)(Cl)] (C^N^N=5,6-diphenyl-2,2'-bipyridine, Pt1) can assemble into nanoaggregates via π-π stacking and complementary hydrogen bonds, rather than Pt-Pt interactions. Pt1 exhibits ratiometric dual emission, including rare blue emission (λ =445 nm) and assembly-induced yellow emission (λ =573 nm), under one- and two-photon excitation. Pt1 displays blue emission in cells with an intact membrane due to its low cellular uptake.

A Mitochondrion-Localized Two-Photon Photosensitizer Generating Carbon Radicals Against Hypoxic Tumors.

The efficacy of photodynamic therapy is typically reliant on the local concentration and diffusion of oxygen. Due to the hypoxic microenvironment found in solid tumors, oxygen-independent photosensitizers are in great demand for cancer therapy. We herein report an iridium(III) anthraquinone complex as a mitochondrion-localized carbon-radical initiator.

An Ultrasmall RuO Nanozyme Exhibiting Multienzyme-like Activity for the Prevention of Acute Kidney Injury.

Oxidative stress induced by reactive oxygen species (ROS) is one of the major pathological mechanisms of acute kidney injury (AKI). Inorganic nanomaterial-mediated antioxidant therapy is considered a promising method for the prevention of AKI; however, currently available antioxidants for AKI exhibit limited clinical efficacy due to the glomerular filtration threshold (∼6 nm). To address this issue, we developed ultrasmall RuO nanoparticles (RuONPs) (average size ≈ 2 nm).

Necroptosis Induced by Ruthenium(II) Complexes as Dual Catalytic Inhibitors of Topoisomerase I/II.

Inducing necroptosis in cancer cells is an effective approach to circumvent drug-resistance. Metal-based triggers have, however, rarely been reported. Ruthenium(II) complexes containing 1,1-(pyrazin-2-yl)pyreno[4,5-e][1,2,4]triazine were developed with a series of different ancillary ligands (Ru1-7).

Rational Design of Cyclometalated Iridium(III) Complexes for Three-Photon Phosphorescence Bioimaging.

Compared to 2PE (two-photon excitation) microscopy, 3PE microscopy has superior spatial resolution, deeper tissue penetration, and less defocused interference. The design of suitable agents with a large Stokes shift, good three-photon absorption (3PA), subcellular targeting, and fluorescence lifetime imaging (FLIM) properties, is challenging. Now, two Ir complexes (3PAIr1 and 3PAIr2) were developed as efficient three-photon phosphorescence (3PP) agents.

Boosting two-photon photodynamic therapy with mitochondria-targeting ruthenium-glucose conjugates.

Herein, we present a series of dual-targeted ruthenium-glucose conjugates that can function as two-photon absorption (TPA) PDT agents to effectively destroy tumors by preferentially targeting both tumor cells and mitochondria. The in vivo experiments revealed an excellent tumor inhibitory efficiency of the dual-targeted TPA PSs.

Lysosome-Targeting Iridium(III) Probe with Near-Infrared Emission for the Visualization of NO/O Crosstalk via In Vivo Peroxynitrite Imaging.

Nitric oxide (NO) and superoxide anions (O) are two noteworthy reactive species implicated in various physiological and pathological processes, such as ROS-induced lysosomal cell death. The interaction ("crosstalk") between them may form a new mediator peroxynitrite (ONOO) which has implications for cancer, diabetes, Alzheimer's disease, and liver-damage. It is therefore essential to investigate lysosomal NO/O crosstalk in vivo through ONOO-responsive molecular tools in order to fully comprehend the physiological and pathological mechanisms involved.

Correction: Fabrication of red blood cell membrane-camouflaged CuSe nanoparticles for phototherapy in the second near-infrared window.

Correction for 'Fabrication of red blood cell membrane-camouflaged Cu2-xSe nanoparticles for phototherapy in the second near-infrared window' by Zhou Liu et al., Chem. Commun.

Correction: Mitochondria-targeted Ir@AuNRs as bifunctional therapeutic agents for hypoxia imaging and photothermal therapy.

Correction for 'Mitochondria-targeted Ir@AuNRs as bifunctional therapeutic agents for hypoxia imaging and photothermal therapy' by Libing Ke et al., Chem. Commun.

Nucleus-targeting ultrasmall ruthenium(iv) oxide nanoparticles for photoacoustic imaging and low-temperature photothermal therapy in the NIR-II window.

Nucleus-targeting NPs based on RuO2 (RuO2NPs) were developed by controlling the size and the surface charge of nanoparticles (NPs). This study not only demonstrates a facile approach for the fabrication of ultrasmall CS-RuO2NPs with good biocompatibility and excellent photothermal properties but also their unique potential for the nucleus-targeted low-temperature PTT.

FerriIridium: A Lysosome-Targeting Iron(III)-Activated Iridium(III) Prodrug for Chemotherapy in Gastric Cancer Cells.

Reported is the Fe -activated lysosome-targeting prodrug FerriIridium for gastric cancer theranostics. It contains a meta-imino catechol group that can selectively bond to, and be oxidized by, free Fe inside the cell. Subsequent oxidative rearrangement releases Fe and hydrolyses the amine bond under acidic conditions, forming an aminobipyridyl Ir complex and 2-hydroxybenzoquinone.

A mitochondria-targeting dinuclear Ir-Ru complex as a synergistic photoactivated chemotherapy and photodynamic therapy agent against cisplatin-resistant tumour cells.

A mitochondria-targeting hetero-binuclear Ir(iii)-Ru(ii) complex was developed as a photoactivated chemotherapy (PACT) and photodynamic therapy (PDT) bifunctional agent to achieve a synergistic effective therapeutic outcome for the therapy of cisplatin-resistant tumour cells.

The stepwise photodamage of organelles by two-photon luminescent ruthenium(ii) photosensitizers.

Ru(ii) polypyridyl complexes, containing a morpholine moiety, and possessing two-photon absorption properties and pH dependent singlet oxygen production were used for stepwise lysosomes-to-mitochondria photodamage of cancer cells.

Mitochondria-targeted Ir@AuNRs as bifunctional therapeutic agents for hypoxia imaging and photothermal therapy.

Ir(iii) complex modified gold nanorods, Ir@AuNRs, were developed as mitochondria-targeted theranostic nanoagents. Their hypoxia imaging and photothermal therapeutic properties were demonstrated in vitro and in vivo.

Bimodal Visualization of Endogenous Nitric Oxide in Lysosomes with a Two-Photon Iridium(III) Phosphorescent Probe.

Nitric oxide (NO) is a fundamental signaling molecule that shows complex effects on the catabolic autophagy process, which is closely linked with lysosomal function. In this study, a new lysosome-targeted, pH-independent, and two-photon phosphorescent iridium(III) complex, , has been investigated for endogenous NO detection and imaging. The rational design of the probe, as the addition of the morpholine moieties and the substitution of a benzyl group in the amino group in , facilitates its accumulation in lysosomes and makes the reaction product with NO, , insusceptible in its phosphorescence intensity and lifetime against pH changes (pH 4-10), well suited for lysosomal NO detection (pH 4-6).