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Nitric oxide (NO) is a crucial signal molecule closely linked to the biological immune response, especially in macrophage polarization. When activated, macrophages enter a pro-inflammatory state and produce NO, a marker for the M1 phenotype. In contrast, the anti-inflammatory M2 phenotype does not produce NO. We developed a mitochondria-targeted two-photon iridium-based complex ( Ir-ImNO ) probe that can detect endogenous NO and monitor macrophages' different immune response states using various imaging techniques, such as one- and two-photon phosphorescence imaging and phosphorescence lifetime imaging. Ir-ImNO was used to monitor the immune activation of macrophages in mice. This technology aims to provide a clear and comprehensive visualization of macrophage immune responses.

Herein, we developed the first metal-based mitochondrial topoisomerase inhibitors to achieve an effective therapeutic outcome for the therapy of cisplatin-resistant tumour cells.

The antiproliferative activity of three cyclometalated Ru(II) complexes with the formula [Ru(bpy) 2 L]PF 6 , where bpy = 2,2'-bipyridine, Ru1: L1 = phenanthro[4,5-fgh]quinoxaline; Ru2: L2 = benzo[f]naphtho[2,1-h]quinoxaline; and Ru3: L3 = phenanthro[9,10-b]pyrazine, have been synthesized and characterized. The lipophilicity of the three Ru(II) complexes was modulated by the alteration of the planarity in the ligands of the complexes. With appropriate lipophilicity, Ru1-Ru3 exhibited mitochondrial accumulating property and cytotoxic activity against a spectrum of cancer cell lines. The underlying mechanism study indicated that these Ru(II) complexes can selectively accumulate in mitochondria and disrupt physiological processes, including the redox balance and energy generation in cancer cells. Elevation of iron content in triple-negative breast cancer (MDA-MB-231 cells) was observed after treatment with Ru(II) complexes, which may contribute to the production of reactive oxygen species (ROS) via Fenton reaction chemistry. Besides, the Ru(II) complexes decreased the intracellular glutathione (GSH) in cancer cells, leading to the failure in the cells to combat oxidative damage. Both of the mentioned processes contribute to the high oxidative stress and eventually lead to cancer cell death. On the other hand, Ru1-Ru3 significantly induced the depletion of adenosine triphosphate (ATP), causing disturbance of energy generation. Moreover, the results of wound-healing assay and transwell invasion assay, as well as the tube formation assay indicated the anti-migration and anti-angiogenesis properties of Ru1-Ru3. Our study demonstrated that these Ru(II) complexes are promising chemotherapeutic agents with oxidative stress induction and energy generation disturbance., (Copyright © 2021. Published by Elsevier Inc.)

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. Its emission is turned on under hypoxic conditions after reduction by reductase. Furthermore, its two-photon excitation properties (λ ex =730 nm) are highly desirable for imaging. Upon irradiation, the reduced form of the complex generates carbon radicals, leading to a loss of mitochondrial membrane potential and cell death (IC 50 light =2.1 μm, IC 50 dark =58.2 μm, PI=27.7). The efficacy of the complex as a PDT agent was also demonstrated under hypoxic conditions in vivo. To the best of our knowledge, it is the first metal-complex-based theranostic agent which can generate carbon radicals for oxygen-independent two-photon photodynamic therapy., (© 2020 Wiley-VCH GmbH.)

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.

Mitochondria are essential organelles in eukaryotic cells, containing various signaling molecules and important enzymes associated with cell growth, death, and proliferation. The visualization of mitochondria and their biochemistry with confocal microscopy, fluorescence (phosphorescence) lifetime microscopy (FLIM, PLIM), and super-resolution microscopy has therefore been of great interest in recent years. In particular, transition metal complexes have emerged as excellent mitochondria-targeting probes, due to their high photostabilities, large Stokes shifts, tunable chemical structures and long luminescence lifetimes. In this review, we focus on platinum, ruthenium and iridium complexes, and their application as detectors of micro-environmental alterations as well as for the imaging of signaling molecules inside mitochondria., 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 © 2019 Elsevier Inc. All rights reserved.)

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.

Iridium complexes were used as a mitochondria-targeting agent to modify the surface of a photothermogenic nanozyme Fe3O4 nanoparticles (Ir@Fe3O4 NPs). Upon NIR irradiation, Ir@Fe3O4 NPs increase the localized temperature to 42 °C which accelerates the catalysis of ˙OH production from H2O2 resulting in excellent mild photothermal therapy.

A hetero-binuclear Ir(iii)-Pt(ii) complex was developed as an antitumor agent. In vitro cytotoxicity results indicated that this complex was effective against cisplatin-resistant tumor cells. Mechanism experiments showed that it can overcome cisplatin resistance by increasing cellular uptake, targeting mitochondria, and inducing cell necrosis.

Two iridium(iii) complexes with ligands containing morpholine groups were used to track mitochondrial pH fluctuation during cell apoptosis as their emissive intensities linearly increased with increase in pH values.

A series of NIR-emitting iridium(iii) complexes were developed for multimodal phosphorescence imaging (NIR imaging, phosphorescence lifetime imaging and time-gated imaging) of mitochondria in living cells, 3D multicellular spheroids (MTCCs) and hippocampus slice under two-photon excitation.

An efficient method was developed that controls biscylometalated iridium(iii) complexes to target mitochondria or lysosomes by regulating the lipophilicity of the main ligands.

In the present study, four mitochondria-specific and two-photon phosphorescence iridium(III) complexes, Ir1-Ir4, were developed for mitochondria imaging in hypoxic tumor cells. The iridium(III) complex has two anthraquinone groups that are hypoxia-sensitive moieties. The phosphorescence of the iridium(III) complex was quenched by the functions of the intramolecular quinone unit, and it was restored through two-electron bioreduction under hypoxia. When the probes were reduced by reductase to hydroquinone derivative products under hypoxia, a significant enhancement in phosphorescence intensity was observed under one- (λ=405 nm) and two-photon (λ=720 nm) excitation, with a two-photon absorption cross section of 76-153 GM at λ=720 nm. More importantly, these probes possessed excellent specificity for mitochondria, which allowed imaging and tracking of the mitochondrial morphological changes in a hypoxic environment over a long period of time. Moreover, the probes can visualize hypoxic mitochondria in 3D multicellular spheroids and living zebrafish through two-photon phosphorescence imaging., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Mitophagy, which is a special autophagy that removes damaging mitochondria to maintain sufficient healthy mitochondria, provides an alternative path for addressing dysfunctional mitochondria and avoiding cellular death. In the present study, by coupling the triphenylamine group with 2-phenylimidazo[4,5-f][1,10]phenanthroline derivatives, we synthesized five Ir(III) complexes with an AIE property that are expected to fulfill requirements for real-time monitoring of mitophagy. Ir1-Ir5 were exploited to image mitochondria with a short incubation time by confocal microscopy and inductive coupled plasma-mass spectrometry (ICP-MS). Due to aggregation-induced emission (AIE), Ir1-Ir5 exhibited excellent photostability compared to MitoTracker Green (MTG). Moreover, Ir1-Ir5 manifested satisfactory photostability in the mitochondrial physiological pH range. In addition, the uptake mechanism of Ir1 was investigated using confocal microscopy and flow cytometry analysis. Finally, using both Ir1 and LysoTracker Green, we were able to achieve real-time monitoring of mitophagy.

Mitochondrial dynamics, including fission and fusion, control the morphology and function of mitochondria, and disruption of mitochondrial dynamics leads to Parkinson's disease, Alzheimer's disease, metabolic diseases, and cancers. Currently, many types of commercial mitochondria probes are available, but high excitation energy and low photo-stability render them unsuitable for tracking mitochondrial dynamics in living cells. Therefore, mitochondrial targeting agents that exhibit superior anti-photo-bleaching ability, deep tissue penetration and intrinsically high three-dimensional resolutions are urgently needed. Two-photon-excited compounds that use low-energy near-infrared excitation lasers have emerged as non-invasive tools for cell imaging. In this work, terpyridyl cyclometalated Ir(III) complexes (Ir1-Ir3) are demonstrated as one- and two-photon phosphorescent probes for real-time imaging and tracking of mitochondrial morphology changes in living cells.

Clinical acceptance of photodynamic therapy is currently hindered by poor depth efficacy and inefficient activation of the cell death machinery in cancer cells during treatment. To address these issues, photoactivation using two-photon absorption (TPA) is currently being examined. Mitochondria-targeted therapy represents a promising approach to target tumors selectively and may overcome the resistance in current anticancer therapies. Herein, four ruthenium(II) polypyridyl complexes (RuL1-RuL4) have been designed and developed to act as mitochondria-targeted two-photon photodynamic anticancer agents. These complexes exhibit very high singlet oxygen quantum yields in methanol (0.74-0.81), significant TPA cross sections (124-198 GM), remarkable mitochondrial accumulation, and deep penetration depth. Thus, RuL1-RuL4 were utilized as one-photon and two-photon absorbing photosensitizers in both monolayer cells and 3D multicellular spheroids (MCSs). These Ru(II) complexes were almost nontoxic towards cells and 3D MCSs in the dark and generate sufficient singlet oxygen under one- and two-photon irradiation to trigger cell death. Remarkably, RuL4 exhibited an IC50 value as low as 9.6 μM in one-photon PDT (λirr = 450 nm, 12 J cm(-2)) and 1.9 μM in two-photon PDT (λirr = 830 nm, 800 J cm(-2)) of 3D MCSs; moreover, RuL4 is an order of magnitude more toxic than cisplatin in the latter test system. The combination of mitochondria-targeting and two-photon activation provides a valuable paradigm to develop ruthenium(II) complexes for PDT applications., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Nitric oxide (NO) is a vitally important cellular messenger molecule related to numerous physiological events and diseases. It is more than 10 years now that mitochondria are suspected to be sources of nitric oxide. Hence, mitochondrial NO tracking probes play an indispensable role in NO behavior analysis. However, a majority of previously reported NO probes can only be employed under one-photon microscopy, often with several drawbacks during application. In the present study, an iridium(III) complex containing 1,10-phenanthroline-5,6-diamine (Ir-Mito-NO) was synthesized and determined to possess high specificity to NO in mitochondria, low cytotoxicity, and rapid and specific "off-on" two-photon phosphorescence. Thus, this complex was developed to image mitochondrial NO levels in living cells, 3D multicellular spheroids and zebrafish., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

A new series of cyclometalated iridium(III) complexes with imidazo[4,5-f][1,10]phenanthroline derivatives (i.e., MitoIr1-MitoIr7) were synthesized and developed to image mitochondria in living cells. In comparison with commercially available mitochondrial trackers, these complexes exhibit a superior capacity to selectively accumulate in mitochondria with no requirement of any membrane permeabilization or replacement of the culture medium. In addition, the excellent photostability under continuous laser irradiation as well as the stable physiological pH resistance of these complexes were confirmed by photobleaching experiments and luminescence measurements. Importantly, MitoIr7, which exhibited both excellent luminescence and high ability to locate in mitochondria, was developed to track the mitochondrial morphological changes over a long period of time.

Endogenous hypochlorite ion (ClO(-)) is a highly reactive oxygen species (ROS) that is produced from hydrogen peroxide and chloride ions catalyzed by myeloperoxidase (MPO). And mitochondrion is one of the major sources of ROS including ClO(-). In the present work, a two-photon phosphorescent probe for ClO(-) in mitochondria was developed. An iridium(III) complex bearing a diaminomaleonitrile group as ClO(-) reactive moiety specifically responded to ClO(-) over other ions and ROSs. When the probe was reacted with ClO(-) to form an oxidized carboxylate product, a significant enhancement in phosphorescence intensity was observed under one-photon (402 nm) and two-photon (750 nm) excitation, with a two-photon absorption cross-section of 78.1 GM at 750 nm. More importantly, ICP-MS results and cellular images co-stained with Mito-tracker Green demonstrated that this probe possessed high specificity for mitochondria. This probe was applied in the one- and two-photon imaging of ClO(-) in vitro and in vivo. The results suggested endotoxin lipopolysaccharide (LPS) induced ClO(-) mostly generated in the liver of zebrafish., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

In the present study, four phosphorescent iridium(III) complexes [Ir(C-N)2(PhenSe)](+) (Ir1-Ir4, in which C-N = 2-(2,4-difluorophenyl)pyridine (dfppy), dibenzo[f,h]quinoxaline (dbq), 2-phenylquinoline (2-pq) and 2-phenylpyridine (ppy), PhenSe = 1,10-phenanthrolineselenazole) with tunable emission colors were developed to image mitochondria and track the dynamics of the mitochondrial morphology. In comparison with commercially available mitochondrial trackers, Ir1-Ir4 possess high specificity to mitochondria in live and fixed cells without requiring prior membrane permeabilization or the replacement of the culture medium. Due to the high resistance of Ir1-Ir4 to the loss of mitochondrial membrane potential as well as the appreciable tolerance to environmental changes, these complexes are applicable for the imaging and tracking of the mitochondrial morphological changes over long periods of time. In addition, Ir2-Ir4 exhibited superior photostability compared to the commercially available mitochondrial trackers. These colorful iridium(III) complexes may contribute to the future development of staining agents for organelle-selective imaging in living cells., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

An AIPE-active iridium(III) complex was found to possess high specificity for mitochondria, superior photostability, low cytotoxicity, and high resistance to the loss of mitochondrial membrane potential. Thus, this complex can be used for mitochondrial imaging and tracking in living cells.

The role of autophagy in cancer development and response to cancer therapy has been a subject of debate. Here we demonstrate that a series of ruthenium(II) complexes containing a β-carboline alkaloid as ligand can simultaneously induce autophagy and apoptosis in tumor cells. These Ru(II) complexes are nuclear permeable and highly active against a panel of human cancer cell lines, with complex 3 displaying activities greater than those of cisplatin. The antiproliferative potentialities of 1-3 are in accordance with their relative lipophilicities, cell membrane penetration abilities, and in vitro DNA binding affinities. Complexes 1-3 trigger release of reactive oxygen species (ROS) and attenuation of ROS by scavengers reduced the sub-G1 population, suggesting ROS-dependent apoptosis. Inhibition of ROS generation also reduces autophagy, indicating that ROS triggers autophagy. Further studies show that suppression of autophagy using pharmacological inhibitors (3-methyladenine and chloroquine) enhances apoptotic cell death.

Two novel unsymmetrical Ir(III) complexes [Ir(ppy)2(N N)Cl2] (N N=2‐(pyrazin‐2‐yl)naphtha[1,2‐e][1,2,4]triazine, Ir1; 2‐(pyrazin‐2‐yl)‐4b,4b'‐dihydroaceanthryleno[1,2‐e][1,2,4]triazine, Ir2) were developed as chemotherapy agents. Ir1 was mainly located in mitochondria. In contrast, Ir2 accumulated in mitochondria but subsequently migrated to the nucleus. Ir1 and Ir2 showed cytotoxicity toward cancerous cells, especially the cisplatin‐resistant ones, indicating their ability to overcome cisplatin resistance. Although both Ir1 and Ir2 disrupted mitochondrial metabolism, they showed different cell death mechanisms. Ir1 induced mitochondria‐mediated apoptosis in cisplatin‐resistant A549R cells. Ir2 was demonstrated to cause PARP‐1 activated necroptosis in A549R cells. This study provides an experimental basis for the rational design of metal‐based chemotherapeutic drugs. [ABSTRACT FROM AUTHOR]

Mitochondria are the control centers of apoptosis. To study mitochondrial dynamics during apoptosis, four phosphorescent fluorinated iridium(iii) complexes (Ir1–Ir4) were designed and synthesized. The complexes' emission maxima, phosphorescent quantum yields, and phosphorescent lifetimes are tuned by the degree of fluorination of the ligand. The complexes exhibit excellent photostability and low (photo)cytotoxicity in HeLa cells. As the complexes are cationic and lipophilic, they localize in mitochondria and enter cells through an energy-independent pathway. In comparison with commercially available mitochondrial trackers (e.g., MTR), Ir1–Ir4 exhibit high specificity to mitochondria even in fixed cells. Due to these outstanding properties, the complexes were successfully used to track mitochondrial dynamics during apoptosis. [ABSTRACT FROM AUTHOR]

Herein we present a series of DCA-Ir(iii) co-drug complexes that preferentially accumulate in mitochondria and selectively cause cancer cell metabolic alterations and were found to act in synergy by sensitizing cancer cells for PDT to achieve cancer-specific enhanced two-photon PDT in the hypoxic environment of multicellular tumor spheroids. [ABSTRACT FROM AUTHOR]

Anticancer, drug delivery, iridium, mitochondria, necroptosis Keywords: anticancer; drug delivery; iridium; mitochondria; necroptosis EN anticancer drug delivery iridium mitochondria necroptosis 1 1 1 05/26/23 20230524 NES 230524 B The Front Cover b shows the synthesis, subcellular localization, and anticancer action mechanism of two novel unsymmetrical Ir(III) complexes, B Ir1 b and B Ir2 b . B Ir1 b induced mitochondria-mediated apoptosis in cisplatin-resistant A549R cells. [Extracted from the article]

Photodynamic therapy (PDT) is an attractive therapeutic modality with high therapeutic efficacy and less side effects compared with other therapies. Herein, we developed a series of cyclometalated IrIII complexes based on 2,2′-biimidazole with different alkyl substitutions (methyl, ethyl, propyl, and butyl). These complexes can efficiently produce singlet oxygen upon light irradiation. In vitro photocytotoxicity towards four cell lines (HeLa, A549, A549R, and LO2) was examined. Ir 1-Ir 5 show quick penetration of cells, remarkable mitochondrial accumulation, strong phototoxicity, and they exhibit high selectivity between tumor cells and normal cells. With the highest 1O2 quantum yields, Ir 5 presents the best PDT efficiency with a high phototoxicity index (PI) value (PI = 150) towards HeLa cells. This work provides a valuable avenue to improve the PDT effect by tuning the lipophilicity and other properties with variation of the alkyl substitution on the photosensitizer. In addition, their satisfying PDT effect to a cisplatin-resistant cell line (A549R) may contribute to the future development of improved chemotherapeutics. [ABSTRACT FROM AUTHOR]

An efficient method was developed that controls biscylometalated iridium(iii) complexes to target mitochondria or lysosomes by regulating the lipophilicity of the main ligands. [ABSTRACT FROM AUTHOR]

In the present study, four mitochondria-specific and two-photon phosphorescence iridium(III) complexes, Ir1- Ir4, were developed for mitochondria imaging in hypoxic tumor cells. The iridium(III) complex has two anthraquinone groups that are hypoxia-sensitive moieties. The phosphorescence of the iridium(III) complex was quenched by the functions of the intramolecular quinone unit, and it was restored through two-electron bioreduction under hypoxia. When the probes were reduced by reductase to hydroquinone derivative products under hypoxia, a significant enhancement in phosphorescence intensity was observed under one- ( λ=405 nm) and two-photon ( λ=720 nm) excitation, with a two-photon absorption cross section of 76-153 GM at λ=720 nm. More importantly, these probes possessed excellent specificity for mitochondria, which allowed imaging and tracking of the mitochondrial morphological changes in a hypoxic environment over a long period of time. Moreover, the probes can visualize hypoxic mitochondria in 3D multicellular spheroids and living zebrafish through two-photon phosphorescence imaging. [ABSTRACT FROM AUTHOR]

Five cyclometalated iridium(III) complexes with 2-phenylimidazo[4,5- f][1,10]phenanthroline derivatives ( IrL1- IrL5) were synthesized and developed to image and track mitochondria in living cells under two-photon (750 nm) excitation, with two-photon absorption cross-sections of 48.8-65.5 GM at 750 nm. Confocal microscopy and inductive coupled plasma-mass spectrometry (ICP-MS) demonstrated that these complexes selectively accumulate in mitochondria within 5 min, without needing additional reagents for membrane permeabilization, or replacement of the culture medium. In addition, photobleaching experiments and luminescence measurements confirmed the photostability of these complexes under continuous laser irradiation and physiological pH resistance. Moreover, results using 3D multicellular spheroids demonstrate the proficiency of these two-photon luminescent complexes in deep penetration imaging. Two-photon excitation using such novel complexes of iridium(III) for exclusive visualization of mitochondria in living cells may substantially enhance practical applications of bioimaging and tracking. [ABSTRACT FROM AUTHOR]

A new series of cyclometalated iridium(iii) complexes with imidazo[4,5-f][1,10]phenanthroline derivatives (i.e., MitoIr1–MitoIr7) were synthesized and developed to image mitochondria in living cells. In comparison with commercially available mitochondrial trackers, these complexes exhibit a superior capacity to selectively accumulate in mitochondria with no requirement of any membrane permeabilization or replacement of the culture medium. In addition, the excellent photostability under continuous laser irradiation as well as the stable physiological pH resistance of these complexes were confirmed by photobleaching experiments and luminescence measurements. Importantly, MitoIr7, which exhibited both excellent luminescence and high ability to locate in mitochondria, was developed to track the mitochondrial morphological changes over a long period of time. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a medical technique that has received increasing attention over the last years for the treatment of cancer due to its high spatiotemporal selectivity and non-invasive nature. However, its therapeutic potential is strongly limited due to the hypoxic environment found in solid tumors which is hampering the production of therapeutically active species. To overcome this drawback, herein, the functionalization of graphitic carbon nitride nanosheets with mitochondria-targeting iridium(III) polypyridine complexes for oxygen self-sufficient two-photon PDT is reported. The nanomaterial was found to synergistically generate O 2 from endogenous H 2 O 2 and H 2 O as well as to produce a mixture of 1O 2 , •OH, and •O 2 - therapeutic species, presenting the ability to tackle hypoxic tumor microenvironments and intervene by a multimodal mechanism through combined type I and type II two-photon PDT. Capitalizing on this, the nanosheets demonstrated to cause significant cellular damage under hypoxic conditions towards monolayer cancer cells as well as three-dimensional multicellular tumor spheroids by combined apoptosis and ferroptosis. The nanomaterial showed to eradicate a hypoxic human melanoma cancer tumor inside a mouse model upon two-photon irradiation at 750 nm within a single treatment. To the best of our knowledge, this study presents the first example of iridium complex functionalized graphitic carbon nitride nanosheets as photosensitizers for the treatment of hypoxic tumors upon clinically relevant two-photon irradiation. [Display omitted] • A facile coordinative modification of g-C 3 N 4 with Ir(III) complexes was developed. • Ir-g-C 3 N 4 is able to sustainably generate O 2 from endogenous H 2 O 2 and H 2 O. • Ir-g-C 3 N 4 is able to produce multiple types of reactive oxygen species and act as a combined type I and type II PDT agent. • Ir-g-C 3 N 4 was found to selectively accumulate in the mitochondria of cancerous cells and induced cell death by combined apoptosis and ferroptosis. [ABSTRACT FROM AUTHOR]

Since the discovery of mitochondrial dynamics, demand for dyes able to track this process has been a great. In contrast to static imaging, dynamic tracking requires superior photostability, low cytotoxicity and high resistance to the loss of mitochondrial membrane potential as well as appreciable tolerance to environmental changes. Recently, a variety of phosphorescent Ir(III) complexes have been found to localize in mitochondria and their applications as mitochondrial dynamics trackers have been assessed in cell monolayers, 3D MCSs and live animals. The examples presented here demonstrate that Ir(III) complexes constitute ideal candidates to meet the challenges of this topic. [ABSTRACT FROM AUTHOR]

Highlights • Organelle-targeting regulating strategies and the characteristics of organelle-targeting metal complexes are summarized. • The bio-applications of organelle-targeting metal complexes are overviewed. • The existing opportunities/challenges of organelle targeting are outlined. Abstract Cellular organelles, such the cytomembrane, lysosome, mitochondrion, Golgi apparatus, the endoplasmic reticulum, and nucleus, play important roles in the normal function of cells. Organelle-targeting bioimaging can aid our understanding of how organelles function, while the development of organelle-targeting therapy could deliver treatment for a variety of diseases. Possessing important advantages such as their photophysical properties, cytotoxicity, and cellular uptake mechanisms, metal complexes for organelle-targeting bio-applications have attracted increasing attention in recent years. In this review, organelle-targeting regulating strategies, and the characteristics of organelle-targeting metal complexes as well as their bio-applications are summarized. Moreover, the existing opportunities/challenges of organelle targeting are outlined and emphasized to inspire the design of a new generation of organelle-targeting metal complexes. [ABSTRACT FROM AUTHOR]

Mitochondrial fission and fusion control the shape, size, number, and function of mitochondria in the cells of organisms from yeast to mammals. The disruption of mitochondrial fission and fusion is involved in severe human diseases such as Parkinson's disease, Alzheimer's disease, metabolic diseases, and cancers. Agents that can real-time track the mitochondrial dynamics are of great importance. However, the short excitation wavelengths and rapidly photo-bleaching properties of commercial mitochondrial dyes render them unsuitable for tracking mitochondrial dynamics. Thus, mitochondrial targeting agents that exhibit superior photo-stability under continual light irradiation, deep tissue penetration and at intrinsically high three-dimensional resolutions are urgently needed. Two-photon-excited compounds employ low-energy near-infrared light and have emerged as a non-invasive tool for real-time cell imaging. Here, cyclometalated Ir(III) complexes ( Ir1–Ir5 ) are demonstrated as one- and two-photon phosphorescent probes for the real-time imaging and tracking of mitochondrial fission and fusion. The results indicate that Ir2 is well suited for two-photon phosphorescent tracking of mitochondrial fission and fusion in living cells and in Caenorhabditis elegans ( C. elegans ). This study provides a practical use for mitochondrial targeting two-photon phosphorescent Ir(III) complexes. [ABSTRACT FROM AUTHOR]

Super-resolution optical microscopy has extended the spatial resolution of cell biology from the cellular level to the nanoscale, enabling the observation of the interactive behavior of single mitochondria and lysosomes. Quantitative parametrization of interactions between mitochondria and lysosomes under super-resolution optical microscopy, however, is currently unavailable, which has severely limited our understanding of the molecular machinery underlying mitochondrial functionality. Here, we introduce an M- value to quantitatively investigate mitochondria and lysosome contact (MLC) and mitophagy under structured illumination microscopy. We found that the M- value for an MLC is typically less than 0.4, whereas in mitophagy it ranges from 0.5 to 1.0. This system permits further investigation of the detailed molecular mechanism governing the interactive behavior of mitochondria and lysosomes. [ABSTRACT FROM AUTHOR]