Search

Abstract Developing single fluorescent probe for simultaneously visualizing mitophagy flux and oxidative stress with super‐resolution is highly demanded yet quite challenging. Herein, a ratiometric HClO probe AHOH is designed and synthesized which is capable of simultaneously staining lysosomes and mitochondria with red and green colour, respectively. AHOH could be selectivity oxidized by HClO, leading to a large emission blue shift (90 nm) and an over 1300‐fold enhancement of the emission ratio of Fl547nm/Fl637nm. We apply AHOH in super‐resolution microscopy and clearly visualize the dynamics of mitochondria–lysosomes interactions and the oxidative stress states upon different stimuli. Mitochondria dysfunction triggered by different drugs and genetic defect lead to elevated oxidative stress and higher levels of mitophagy. Moreover, AHOH could serve as a reliable tool for evaluating the efficacy of drugs regulating mitochondria dysfunction. This work provides a powerful dual‐colour super‐resolution imaging agent for real‐time monitoring the dynamics of organelle interactions and oxidative stress.

Abstract Organelles are specialized areas where cells perform specific processes necessary for life and actively communicate with each other to keep the whole cell functioning. Disorders of the organelle networks are associated with multiple pathological processes. However, clearly and intuitively visualizing the highly dynamic interactions between ultrafine organelles is challenging. Fluorescence imaging technology provides opportunities due to the distinct advantages of facile, non‐invasiveness and dynamic detection, making it particularly well‐suited for applications in uncovering the mysterious veil of organelle interactions. Regrettably, the lack of ideal fluorescence agents has always been an obstacle in imaging the intricate behaviors of organelles. In this review, we provide a systematic discussion on the existing dual‐color and dual‐targetable molecular sensors used in monitoring organelle interactions, with a specific focus on their targeting strategies, imaging mechanisms and biological applications. Additionally, the current limitations and future development directions of dual‐targetable probes and dual‐emissives are briefly discussed. This review aims to provide guidance for researchers to develop more improved probes for studying organelle interactions in the biomedical field.

Abstract Glutamine synthetase (GS) is vital in maintaining ammonia and glutamate (Glu) homeostasis in living organisms. However, the natural enzyme relies on adenosine triphosphate (ATP) to activate Glu, resulting in impaired GS function during ATP-deficient neurotoxic events. To date, no reports demonstrate using artificial nanostructures to mimic GS function. In this study, we synthesize aggregation-induced emission active polyP-Mn nanosheets (STPE-PMNSs) based on end-labeled polyphosphate (polyP), exhibiting remarkable GS-like activity independent of ATP presence. Further investigation reveals polyP in STPE-PMNSs serves as phosphate source to activate Glu at low ATP levels. This self-feeding mechanism offers a significant advantage in regulating Glu homeostasis at reduced ATP levels in nerve cells during excitotoxic conditions. STPE-PMNSs can effectively promote the conversion of Glu to glutamine (Gln) in excitatory neurotoxic human neuroblastoma cells (SH-SY5Y) and alleviate Glu-induced neurotoxicity. Additionally, the fluorescence signal of nanosheets enables precise monitoring of the subcellular distribution of STPE-PMNSs. More importantly, the intracellular fluorescence signal is enhanced in a conversion-responsive manner, allowing real-time tracking of reaction progression. This study presents a self-sustaining strategy to address GS functional impairment caused by ATP deficiency in nerve cells during neurotoxic events. Furthermore, it offers a fresh perspective on the potential biological applications of polyP-based nanostructures.

Metal complexes for anti-tumor treatment have been developed rapidly in recent decades since the application of cisplatin in clinics. However, some tumor cells are resistant to apoptosis and not sensitive to metallodrugs that function through the apoptotic pathway. Recently, metal complexes have been reported to cause ferroptosis against tumor cells, which offers new opportunities for anticancer therapy. In this perspective, ferroptosis-inducing metal complexes and their working mechanisms are introduced, while the challenges and opportunities are also discussed.

Aggregation induced emission luminogen (AIEgen) based photosensitizers (PSs) have been developed for photodynamic cancer therapy. Here the authors report a series of AIEgen-based PSs that selectively target the Golgi apparatus, showing enhanced singlet oxygen generation and photodynamic therapy performance in cancer models.

Abstract Kasha's rule, which states that all exciton emissions occur from the lowest excited state and are independent of excitation energy, makes high‐energy excitons difficult to use and severely hinders the widespread applications of organic photoluminescent materials in the real world. For decades, scientists have tried to break this rule to unleash the power of high‐energy excitons, but only minimal progress has been achieved, with no rational guiding principles provided, and few applications developed. So far, breaking Kasha's rule has remained a purely academic concept. In this paper, we introduce a design principle for a purely organic anti‐Kasha system and synthesise a series of compounds based on the design rule. As predicted, these compounds all display evident S2 emissions in dilute solutions. In addition, we introduce a highly accurate (over 90%) convolutional neural network as an assistant for the classification of cells using anti‐Kasha luminogens, thereby providing a new application direction for anti‐Kasha systems.

Mitochondrial function is important for muscle maintenance and function, and mitochondrial proteolysis maintains mitochondrial integrity and function. Here the authors report that that loss of LONP1-dependent mitochondrial proteolysis in muscle causes reduced muscle mass and strength via activation of autophagy.

Most fluorescence probes to measure hypoxia are irreversible. Here, the authors develop a near infrared luminescent probe to measure hypoxia which is reversible and use the probe to monitor hypoxia-reoxygenation in several animal models.

J-aggregation has been proved to be an efficient strategy for the development of fluorescent imaging agents in the NIR-II spectral region but the design of appropriate J-aggregates is challenging. Here, the authors demonstrate J-aggregation of a BODIPY dye with NIR-II emission and demonstrate lymph node imaging for fluorescence guided surgery.

The endoplasmic reticulum (ER) is the main storage site of Zn2+, and Zn2+ plays an important role in regulating ER homeostasis. Therefore, we designed and synthesized a ratiometric fluorescent Zn2+ probe ER-Zn targeting ER stress. The probe displayed a specific Zn2+ induced blue shift at the spectral maximum values of excitation (80 nm) and emission (30 nm). The ratio imaging capability of Zn2+ under dual excitation mode can be applied not only to quantitative and reversible detection of exogenous Zn2+, but also the observation of the Zn2+ level change under ER stress, elucidating the different behaviors of Zn2+ release in ER stimulated by tunicamycin and thapsigargin. Additionally, the NIR imaging capability of ER-Zn provides an important basis for further research on animal models and is expected to realize the visualization and treatment of ER stress-related diseases through the regulation of ER stress by Zn2+. We envision that this probe can be applied to screen drugs for diseases related to ER stress regulation.

Subcellular Zn2+ compartmentalisation is essential for cell biology. Here the authors make a turn-on fluorescent Zn2+ probe that localises to multiple organelles, and correlate its location using organelle morphology derived from structured illumination microscopy.

Cationic, water-soluble benzophenothiaziniums have been recognized as effective type I photosensitizers (PSs) against hypoxic tumor cells. However, the study of the structure–property relationship of this type of PS is still worth further exploration to achieve optimized photodynamic effects and minimize the potential side effects. Herein, we synthesized a series of benzophenothiazine derivatives with minor N-alkyl alteration to study the effects on the structure–property relationships. The cellular uptake, subcellular organelle localization, reactive oxygen species (ROS) generation, and photocytotoxicity performances were systematically investigated. NH2NBS and EtNBS specifically localized in lysosomes and exhibited high toxicity under light with a moderate phototoxicity index (PI) due to the undesirable dark toxicity. However, NMe2NBS with two methyl substitutions accumulated more in mitochondria and displayed an excellent PI value with moderate light toxicity and negligible dark toxicity. Without light irradiation, NH2NBS and EtNBS could induce lysosomal membrane permeabilization (LMP), while NMe2NBS showed no obvious damage to lysosomes. After irradiation, NH2NBS and EtNBS were released from lysosomes and relocated into mitochondria. All compounds could induce mitochondria membrane potential (MMP) loss and nicotinamide adenine dinucleotide phosphate (NADPH) consumption under light to cause cell death. NMe2NBS exhibited remarkable in vivo photodynamic therapy (PDT) efficacy in a xenograft mouse tumor (inhibition rate, 89%) with no obvious side effects. This work provides a valuable methodology to investigate the structure–property relationships of benzophenothiazine dyes, which is of great importance in the practical application of PDT against hypoxia tumor cells.

Biothiols, including glutathione (GSH), homocysteine (Hcy) and cysteine (Cys), play crucial roles in various physiological processes. Though an array of fluorescent probes have been designed to visualize biothiols in living organisms, few one-for-all imaging agents for sensing biothiols with fluorescence and photoacoustic imaging capabilities have been reported, since instructions for synchronously enabling and balancing every optical imaging efficacy are deficient. Herein, a new near-infrared thioxanthene-hemicyanine dye (Cy-DNBS) has been constructed for fluorescence and photoacoustic imaging of biothiols in vitro and in vivo. Upon treatment with biothiols, the absorption peak of Cy-DNBS shifted from 592 nm to 726 nm, resulting in a strong NIR absorption as well as a subsequent turn-on PA signal. Meanwhile, the fluorescence intensity increased instantaneously at 762 nm. Then, Cy-DNBS was successfully utilized for imaging endogenous and exogenous biothiols in HepG2 cells and mice. In particular, Cy-DNBS was employed for tracking biothiols upregulation in the liver of mice triggered by S-adenosyl methionine by means of fluorescent and photoacoustic imaging methods. We expect that Cy-DNBS serves as an appealing candidate for deciphering biothiols-related physiological and pathological processes.

Photodynamic therapy (PDT) has attracted much attention in the field of anticancer treatment. However, PDT has to face challenges, such as aggregation caused by quenching of reactive oxygen species (ROS), and short 1O2 lifetime, which lead to unsatisfactory therapeutic effect. Aggregation-induced emission luminogen (AIEgens)-based photosensitizers (PSs) showed enhanced ROS generation upon aggregation, which showed great potential for hypoxic tumor treatment with enhanced PDT effect. In this review, we summarized the design strategies and applications of AIEgen-based PSs with improved PDT efficacy since 2019. Firstly, we introduce the research background and some basic knowledge in the related field. Secondly, the recent approaches of AIEgen-based PSs for enhanced PDT are summarized in two categories: (1) organelle-targeting PSs that could cause direct damage to organelles to enhance PDT effects, and (2) PSs with tumor-targeting abilities to selectively suppress tumor growth and reduce side effects. Finally, current challenges and future opportunities are discussed. We hope this review can offer new insights and inspirations for the development of AIEgen-based PSs for better PDT effect.

Zn2+ is a vital ion for most of the physiological processes in the human body, and it usually has a mutual effect with oxidative stress that often occurs in pathological tissues. Detecting fluctuation of Zn2+ level in cells undergoing oxidative stress could be beneficial to understanding the relationship between them. Herein, a ratiometric fluorescent Zn2+ probe was rationally designed. The wavelength corresponding to the maximum fluorescence intensity bathometrically shifted from 620 nm to 650 nm after coordinating with Zn2+. The intensity ratio of two fluorescence channels changed significantly in cells treated by oxidative stress inducers. It was shown from the results that the labile zinc level was generally elevated under oxidative stress stimulated by various inducers.

The development of intelligent materials, in particular those showing the highly sensitive mechanoresponsive luminescence (MRL), remains challenging. Here the authors report a strategy for constructing high performance On-Off MRL materials by introducing nitrophenyl groups to molecules with aggregation-induced emission characteristic.

Photodynamic therapy (PDT) often faces challenges such as oxygen dependence and limited tumour specificity. We report a tumour-targeting photosensitizer (PS), RUCXB, which enhances uptake by cancer cells by targeting overexpressed cyclooxygenase-2 enzyme in tumours. RUCXB also reduces oxygen dependence via a type I PDT mechanism and achieves a strong therapeutic effect through the synergistic induction of ferroptosis and apoptosis. This work presents a reliable strategy for developing potent PSs with enhanced PDT efficacy, tumour selectivity, and diminished oxygen dependence. [ABSTRACT FROM AUTHOR]