An artesunate-modified half-sandwich iridium(iii) complex inhibits colon cancer cell proliferation and metastasis through the STAT3 pathway.

Colon cancer is one of the most commonly diagnosed cancers and is recognized as the most aggressive tumor of the digestive system. Aberrant activation of signal transducer and activator of transcription 3 (STAT3) is associated with proliferation, metastasis and immunosuppression of the tumor cells. Here, to inhibit the STAT3 pathway and suppress metastasis in colon cancer cells, the half-sandwich iridium complex Ir-ART containing an artesunate-derived ligand was synthesized.

Molecular probes for tracking lipid droplet membrane dynamics.

Lipid droplets (LDs) feature a unique monolayer lipid membrane that has not been extensively studied due to the lack of suitable molecular probes that are able to distinguish this membrane from the LD lipid core. In this work, we present a three-pronged molecular probe design strategy that combines lipophilicity-based organelle targeting with microenvironment-dependent activation and design an LD membrane labeling pro-probe called LDM. Upon activation by the HClO/ClO microenvironment that surrounds LDs, LDM pro-probe releases LDM-OH probe that binds to LD membrane proteins thus enabling visualization of the ring-like LD membrane.

Light switchable Ir(III)-based photosensitizers: a dual-state system for non-invasive, reversible ROS control in tumor therapy.

Photodynamic therapy (PDT), a powerful anticancer approach converting oxygen to ROS for tumor ablation, encounters hurdles like limited spatio-temporal selectivity and the consequent unnecessary damage to normal tissues. Addressing these challenges, developing controllable Ir(III)-based photosensitizers (PSs) emerges as a promising solution, offering enhanced efficacy and precision in cancer therapy, while propelling the clinical progression of metal-based PSs. Herein, we proposed a series of light-controlled PSs, integrating an Ir(III)-based moiety with a light-responsive module, enabling non-invasive "off-on" control of ROS production efficient energy transfer.

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-Targeting Metallodrugs for Cancer Therapy: Perspectives from Cell Death Modes.

Mitochondria, recognized as the cellular powerhouses, are indispensable organelles responsible for crucial cellular processes, such as energy metabolism, material synthesis, and signaling transduction. Their intricate involvement in a broad spectrum of diseases, particularly cancer, has propelled the exploration of mitochondria-targeting treatment as a promising strategy for cancer therapy. Since the groundbreaking discovery of cisplatin, the trajectory of research on the development of metal complexes have been marked by continuous advancement, giving rise to a diverse array of metallodrugs characterized by variations in ligand types, metal center properties, and oxidation states.

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.

Iridium(III)-Based PD-L1 Agonist Regulates p62 and ATF3 for Enhanced Cancer Immunotherapy.

Anti-PD-L1 immunotherapy, a new lung cancer treatment, is limited to a few patients due to low PD-L1 expression and tumor immunosuppression. To address these challenges, the upregulation of PD-L1 has the potential to elevate the response rate and efficiency of anti-PD-L1 and alleviate the immunosuppression of the tumor microenvironment. Herein, we developed a novel usnic acid-derived Iridium(III) complex, , that boosts PD-L1 expression and converts "cold tumors" to "hot".

Dual inhibition of oxidative phosphorylation and glycolysis to enhance cancer therapy.

Dual suppression of oxidative phosphorylation (OXPHOS) and glycolysis can disrupt metabolic adaption of cancer cells, inhibiting energy supply and leading to successful cancer therapy. Herein, we have developed an α-tocopheryl succinate (α-TOS)-functionalized iridium(III) complex Ir2, a highly lipophilic mitochondria targeting anticancer molecule, could inhibit both oxidative phosphorylation (OXPHOS) and glycolysis, resulting in the energy blockage and cancer growth suppression. Mechanistic studies reveal that complex Ir2 induces reactive oxygen species (ROS) elevation and mitochondrial depolarization, and triggers DNA oxidative damage.

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.

Recent advances in Zn imaging: From organelles to in vivo applications.

Zn is involved in various physiological and pathological processes in living systems. Monitoring the dynamic spatiotemporal changes of Zn levels in organelles, cells, and in vivo is of great importance for the investigation of the physiological and pathological functions of Zn. However, this task is quite challenging since Zn in living systems is present at low concentrations and undergoes rapid dynamic changes.

Fluorescent Probes for Biological Species and Microenvironments: from Rational Design to Bioimaging Applications.

Some important biological species and microenvironments maintain a complex and delicate dynamic balance in life systems, participating in the regulation of various physiological processes and playing indispensable roles in maintaining the healthy development of living bodies. Disruption of their homeostasis in living organisms can cause various diseases and even death. Therefore, real time monitoring of these biological species and microenvironments during different physiological and pathological processes is of great significance.

An ER-targeted "reserve-release" fluorogen for topological quantification of reticulophagy.

The endoplasmic reticulum's (ER) dynamic nature, essential for maintaining cellular homeostasis, can be influenced by stress-induced damage, which can be assessed by examining the morphology of ER dynamics and, more locally, ER properties such as hydrophobicity, viscosity, and polarity. Although numerous ER-specific chemical probes have been developed to monitor the ER's physical and chemical parameters, the quantitative detection and super-resolution imaging of its local hydrophobicity have yet to be explored. Here, we describe a photostable ER-targeted probe with high signal-to-noise ratio for super-resolution imaging that can specifically respond to changes in ER hydrophobicity under stress based on a "reserve-release" mechanism.

Light-activated mitochondrial fission through optogenetic control of mitochondria-lysosome contacts.

Mitochondria are highly dynamic organelles whose fragmentation by fission is critical to their functional integrity and cellular homeostasis. Here, we develop a method via optogenetic control of mitochondria-lysosome contacts (MLCs) to induce mitochondrial fission with spatiotemporal accuracy. MLCs can be achieved by blue-light-induced association of mitochondria and lysosomes through various photoactivatable dimerizers.

Single Image Capture of Bioactive Ion Crosstalk within Inter-Organelle Membrane Contacts at Nanometer Resolution.

Rapid bioactive ion exchange is a form of communication that regulates a wide range of biological processes. Despite advances in super-resolution optical microscopy, visualizing ion exchange remains challenging due to the extremely fast nature of these events. Here, a "converting a dynamic event into a static image construction" (CDtSC) strategy is developed that uses the color transformation of a single dichromatic molecular probe to visualize bioactive ion inter-organelle exchange in live cells.

A ratiometric pH probe for acidification tracking in dysfunctional mitochondria and tumour tissue .

Cellular dysregulated pH and mitochondrial metabolism are commonly two central factors for solid tumour progression. pH regulation and long-term mitochondrial tracking provide a great opportunity for tumour treatment. pH probes with suitable p and satisfactory mitochondria-immobilizing character are demanded for tumour recognition and therapy.

An Endoplasmic Reticulum-Targeted Ratiometric Fluorescent Molecule Reveals Zn Micro-Dynamics During Drug-Induced Organelle Ionic Disorder.

The endoplasmic reticulum (ER) is the main storage site of Zn, and Zn plays an important role in regulating ER homeostasis. Therefore, we designed and synthesized a ratiometric fluorescent Zn probe ER-Zn targeting ER stress. The probe displayed a specific Zn induced blue shift at the spectral maximum values of excitation (80 nm) and emission (30 nm).

Platinum-Based Two-Photon Photosensitizer Responsive to NIR Light in Tumor Hypoxia Microenvironment.

Platinum-based photosensitizers are promising anticancer agents in photodynamic therapy. The cytotoxic effects primarily arise from the production of singlet oxygen and platination of DNA. However, their efficacy is limited by drug resistance and hypoxic tumor microenvironment.

Optical properties of natural small molecules and their applications in imaging and nanomedicine.

Natural small molecules derived from plants have fascinated scientists for centuries due to their practical applications in various fields, especially in nanomedicine. Some of the natural molecules were found to show intrinsic optical features such as fluorescence emission and photosensitization, which could be beneficial to provide spatial temporal information and help tracking the drugs in biological systems. Much efforts have been devoted to the investigation of optical properties and practical applications of natural molecules.

Rational construction of a reversible arylazo-based NIR probe for cycling hypoxia imaging in vivo.

Reversible NIR luminescent probes with negligible photocytotoxicity are required for long-term tracking of cycling hypoxia in vivo. However, almost all of the reported organic fluorescent hypoxia probes reported until now were irreversible. Here we report a reversible arylazo-conjugated fluorescent probe (HDSF) for cycling hypoxia imaging.

Ferroptosis Photoinduced by New Cyclometalated Iridium(III) Complexes and Its Synergism with Apoptosis in Tumor Cell Inhibition.

Limited therapeutic efficacy to hypoxic and refractory solid tumors has hindered the practical application of photodynamic therapy (PDT). Two new benzothiophenylisoquinoline (btiq)-derived cyclometalated Ir complexes, IrL1 and MitoIrL2, were constructed as potent photosensitizers, with the latter being designed for mitochondria accumulation. Both complexes demonstrated a type I PDT process and caused photoinduced ferroptosis in tumor cells under hypoxia.

Simultaneous Zn tracking in multiple organelles using super-resolution morphology-correlated organelle identification in living cells.

Zn plays important roles in metabolism and signaling regulation. Subcellular Zn compartmentalization is essential for organelle functions and cell biology, but there is currently no method to determine Zn signaling relationships among more than two different organelles with one probe. Here, we report simultaneous Zn tracking in multiple organelles (Zn-STIMO), a method that uses structured illumination microscopy (SIM) and a single Zn fluorescent probe, allowing super-resolution morphology-correlated organelle identification in living cells.

A dual-labeling probe to track functional mitochondria-lysosome interactions in live cells.

Mitochondria-lysosome interactions are essential for maintaining intracellular homeostasis. Although various fluorescent probes have been developed to visualize such interactions, they remain unable to label mitochondria and lysosomes simultaneously and dynamically track their interaction. Here, we introduce a cell-permeable, biocompatible, viscosity-responsive, small organic molecular probe, Coupa, to monitor the interaction of mitochondria and lysosomes in living cells.

Photoinduced synergistic cytotoxicity towards cancer cells Ru(II) complexes.

Ru(ii) complexes have been recognized as excellent anticancer candidates. However, the poor cell uptake of these complexes has been the major obstacle in improving their anticancer efficacy. Along with the development of the knowledge on the anticancer nature of the Ru(ii) complexes, several strategies have been designed to increase the cellular accumulation of these complexes.