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DYES AND PIGMENTS · 2025 · IF 4.2

In vivo tracking of hepatic cathepsin B in diabetes using a sulfur-modified hemicyanine-based activatable imaging probe

Ningxi Wu,Sirui Hang,Shuying Chen,Kai Wang,Yue Zheng

We report the design and synthesis of CatP, a sulfur-substituted hemicyanine-based activatable probe, for the sensitive detection of cathepsin B (CatB) activity. This probe was applied to study the dynamic changes of hepatic CatB in diabetic mellitus (DM), a prevalent metabolic disease. The probe incorporates a Val-Cit linker specifically cleaved by CatB, triggering an intramolecular charge transfer (ICT) mechanism that generates strong near-infrared (750 nm) fluorescence and photoacoustic signals. Structural optimization through sulfur substitution significantly enhanced photoacoustic signal intensity compared to conventional oxygen-substituted analogs. In diabetic mouse models, CatP revealed significantly elevated hepatic CatB activity, which was normalized by metformin treatment as confirmed by both in vivo imaging and ex vivo immunofluorescence. Comprehensive biosafety evaluation demonstrated excellent biocompatibility with >90 % cell viability and no observable organ toxicity. These findings establish sulfur-modified hemicyanine as a promising scaffold for developing high-performance activatable probes, and demonstrate the value of CatP as a functional dye for studying protease activity in biomedical research.

研究领域: 分子影像学 · 生物医学工程 · 糖尿病研究 · 蛋白酶生物学 · 光学成像 · 诊疗一体化
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY · 2025 · IF 4.6

A sulfur-substituted hemicyanine-based activatable probe for photoacoustic visualization of neutrophil elastase in liver I/R injury

Kai Wang,Yan-Ru Wang,Jun Zhao,Ren-Min Zhou,Xi-Feng Xu,Tong Wang,Zhong-Yuan Cheng

Hepatic ischemia-reperfusion (I/R) injury is a major clinical complication, and the precise monitoring of key inflammatory mediators like neutrophil elastase (NE) in vivo remains a significant challenge. To address this, we developed HDS-NE, a highly specific and activatable molecular probe based on a sulfur-substituted hemicyanine scaffold, engineered for the simultaneous detection of NE via fluorescence and photoacoustic imaging modalities. The probe demonstrated exceptional sensitivity and selectivity toward NE, enabling the real-time visualization of elevated NE activity in a murine model of hepatic I/R injury. Both in vivo and ex vivo imaging results confirmed a markedly enhanced signal in injured livers compared to controls, which was further validated by serum assays and histology. Crucially, this study represents the successful achievement of non-invasive, in vivo imaging of NE activity during hepatic I/R processes, offering a powerful tool for diagnosing and studying inflammatory liver diseases.

研究领域: 分子影像学 · 炎症研究 · 肝脏病学 · 生物医学工程 · 光学成像
✓ 已验证 DOI PubMed 高影响因子
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SENSORS AND ACTUATORS B-CHEMICAL · 2017 · IF 5.401

A novel turn-on fluorescent probe for cyanide detection in aqueous media based on a BODIPY-hemicyanine conjugate

Yanhua Yu,Tingting Shu,Bingjie Yu,Yun Deng,Cheng Fu,Yangguan Gao,Changzhi Dong,Yibin Ruan

A novel BODIPY-hemicyanine based fluorescent probe 1 for cyanide (CN − ) detection was designed and synthesized. Among the tested anions, the probe showed high selectivity towards CN − . Only addition of CN − to probe 1 in aqueous solution (V H2O /V EtOH   =   1/1) could result in a remarkable blue shift of the absorption band from 385   nm to 265   nm and induce 20-fold fluorescence enhancement at 515   nm. The sensing mechanism was based on nucleophilic addition between CN − and indolium group, which was confirmed by 1 H NMR and mass spectrum analysis. Plot of fluorescence intensity as a function of CN − concentrations exhibited a good linear relationship in the range of 0–10   μM, with a detection limit to be 1.53   ppb. Moreover, the proposed sensing approach could work in a wide pH range from 5.0–9.0 and reach an equilibrium instantaneously. Finally, probe 1 was successfully applied in detection of CN − in natural water samples and on test paper strips with satisfactory results.

研究领域: 分析化学 · 环境科学 · 生物医学
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Advanced Healthcare Materials · 2023 · IF 10

Near-Infrared Ii Hemicyanine Dye with Large Stokes Shift Designed by Tict Regulation for Boosting Imaging-Guided Photothermal Therapy

Liang Zhao,Han Zhu,You-Yang Duo,Dai-Wen Pang,Zhi-Gang Wang,Shu-Lin Liu

The serious threat that cancer poses to human health highlights the significance of early detection and effective treatment. The integration of fluorescence diagnosis and photothermal therapy in NIR-II has gained attention due to its high sensitivity, fast response, and non-invasiveness. Fluorescence, produced by the radiative relaxation process of electrons in a molecule, and photothermal, generated by the non-radiative relaxation process of electrons in a molecule, are competing photophysical processes. Hence, it is a challenge for the molecule to balance between the properties of fluorescence and photothermal. In this study, we designed a NIR-II hemicyanine with TICT character to obtain molecules with both better fluorescence and photothermal properties, utilizing positively charged pyridine salt and triphenylamine as electron acceptor and donor, respectively, and oxole as the conjugated π-bridge. HCY-995 , one of the synthesized compounds, had a quantum yield of 0.09%, photothermal conversion efficiency of 54.90%, and a significant Stoke shift of 232 nm, which made it appropriate for the integration of photothermal therapy and high-resolution imaging. This study provides new insights into the development of NIR-II molecules with fluorescent and photothermal integrated properties. This article is protected by copyright. All rights reserved

研究领域: 生物医学工程 · 分子影像 · 癌症治疗
✓ 已验证 DOI PubMed 高影响因子
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ANALYTICA CHIMICA ACTA · 2025 · IF 6

Synthesis of a hemicyanine-based near-infrared fluorescent probe for the diagnosis of pulmonary fibrosis and acute lung injury

Lu Fan,Yun Guo,Zhen-Zhen Pan,Shuai Ying,Zhong-Yuan Cheng,Kai Wang,Ling Li

Background Pulmonary fibrosis (PF) and acute lung injury (ALI) are severe and often fatal pulmonary conditions with high morbidity and limited treatment options, characterized by progressive interstitial scarring or acute diffuse alveolar damage, respectively. Mitochondrial dysfunction is increasingly implicated in their pathogenesis, and LACTB (Lactamase beta), a mitochondrial serine protease, is a potential regulator of these. However, current diagnostics cannot capture early molecular or organelle-level changes. This gap highlights the need for a noninvasive, mitochondria-targeted imaging approach to monitor disease-related biochemical alterations in vivo . Results HD-LACTB is a hemicyanine-based Near-Infrared (NIR) fluorescent probe, whose activation is triggered by enzymatic bond cleavage. LACTB recognizes the peptide sequence within the probe and catalyzes hydrolysis at the cleavage site, releasing a free hemicyanine fluorophore and the corresponding peptide fragment. It features emission in the NIR spectrum (725 nm) for enhanced tissue penetration, along with high selectivity for LACTB and low cytotoxicity, outperforming previous fluorescent probes. The cationic hemicyanine moiety drives selective mitochondrial accumulation, ensuring that the fluorescence signal specifically reports mitochondrial LACTB activity in cells. In murine models of PF and ALI (bleomycin- and LPS-induced, respectively), systemic administration of HD-LACTB enabled noninvasive lung imaging with robust, organ-specific NIR signals. The probe readily distinguished fibrotic or acutely injured lungs from normal controls by visualizing LACTB-mediated metabolic alterations, with fluorescence intensities correlating with disease severity, thereby improving diagnostic precision over prior non-targeted imaging approaches. Significance The development of HD-LACTB showcases a conceptual advance in probe design: a mitochondria-targeted, enzyme-responsive NIR fluorophore that bridges a critical gap in lung disease imaging. This strategy illustrates how rationally engineered chemical probes can provide unprecedented molecular specificity in vivo , heralding a new class of materials-based diagnostics for respiratory diseases. By enabling precise, noninvasive visualization of pathological processes at the organelle level, HD-LACTB paves the way for innovative diagnostic approaches in pulmonary medicine.

研究领域: 生物医学成像 · 呼吸医学 · 分子诊断学 · 化学生物学 · 线粒体生物学
✓ 已验证 DOI PubMed 高影响因子
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DYES AND PIGMENTS · 2024 · IF 4.1

Heavy atom-modified hemicyanine dyes as photosensitizer scaffolds combined with nitric oxide trigger the butterfly effect in tumor therapy

Zhijia Sheng,Chao Zhao,Xiaoyan Huang,Jing Wang,Yi Liu

Hypoxia is a common feature of solid tumors and is considered to be the fatal flaw of conventional photodynamic therapy (PDT), which severely reduces the overall therapeutic efficacy. Here, we developed a series of halogenated photosensitizers to address this issue. The results showed that the introduction of heavy atoms enhanced the spin-coupling effect of the photosensitizers and effectively improved the type I PDT (non-oxygen-dependent) efficiency. The preferred iodine-substituted photosensitizer NRh–I was used as the basic architecture, and further nitrosyl modification was performed to obtain the NO small-molecule prodrug, which was finally encapsulated with DSPE-mPEG 5k to obtain a biocompatible NO nanophotocontrolled prodrug. By using the enhanced permeability and retention effect (EPR), the prodrug system can precisely target the lesion site, release a high concentration of NO by photocontrol, kill the tumor cells, and at the same time, cascade with ROS released with the same “time-space” precision to generate higher cytotoxicity, ONOO − , which generates a stronger targeted synergistic therapeutic effect. This “butterfly effect” strategy maximizes the effect of PDT and broadens the idea of translational medicine.

研究领域: 癌症治疗 · 药学 · 生物医学工程 · 化疗
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ADVANCED FUNCTIONAL MATERIALS · 2024 · IF 18.5

Donor Substitution Engineering of Hemicyanine Nanoparticles to Reprogram the Tumor Microenvironment and Enhance Fn14-Targeted BiTE for Glioblastoma Photoimmunotherapy

Gaowei Li,Shichao Jiang,Zongliang Zhang,Xiaoyin Liu,Kai Wu,Peng Liu,Mei Yang,Ting Zhou,Jiamei Xiao,Nini Xin,Xiaoyang Wu,Zhihong Chen,Jie Ding,Chengheng Wu,Dan Wei,Jing Sun,Aiping Tong,Hongsong Fan,Liangxue Zhou

Glioblastoma (GBM) is a highly malignant intracranial tumor with limited treatment options. Bispecific T-cell engagers (BiTEs) are being explored for GBM treatment, but their success is hindered by inadequate T cell infiltration and activation due to the acidic and immunosuppressive microenvironment. Photothermal immunotherapy lyses tumors and activates immune responses, complementing BiTEs. This study innovatively employs a donor engineering strategy to develop hemicyanine dyes (Hcys) that emit from near-infrared (NIR) I to NIR II. The Hcy with excellent properties is encapsulated in an amphiphilic micelle, forming a nano assembly with lactate oxidase (PLH1100). PLH1100 exhibits spectral absorption at 980 nm, a photothermal conversion efficiency of 58.7%, and capability for NIR-II tumor imaging. Besides photothermal tumor ablation, PLH1100 regulates lactic acid metabolism and activates immunogenic cell death, improving the tumor microenvironment and promoting T cell infiltration and activation. Further studies demonstrate PLH1100 effectively kills human and murine GBM cells, inhibits orthotopic U87 tumor growth in BALB/c-nu mice, and enhances the efficacy of Fn14-targeted BiTE in orthotopic GL261 tumors in C57BL/6 mice, achieving a synergistic “1+1>2” therapeutic effect. Collectively, this work opens a new pathway for using Hcy-based molecules combined with BiTE drugs for GBM therapy, with significant clinical potential.

研究领域: 肿瘤学 · 纳米技术 · 免疫疗法 · 分子生物学 · 神经科学
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JOURNAL OF HAZARDOUS MATERIALS · 2017 · IF 6.065

A novel “turn-on” fluorescent probe based on triphenylimidazole-hemicyanine dyad for colorimetric detection of CN− in 100% aqueous solution

Shuzhi Liu,Min Yang,Yijiang Liu,Hongbiao Chen,Huaming Li

A new colorimetric fluorescent probe (MCy) for CN − is designed and synthesized based on triphenylimidazole-hemicyanine dyad. The probe shows high selectivity towards CN − in 100% aqueous solution even in the presence of other competitive anions such as F − , Cl − , AcO − , NO 2 − , H 2 PO 4 − , I − , SCN − , SO 4 2− , NO 3 − , HCO 3 − , Br − and S 2− . Upon nucleophilic addition of CN − to the indolium group, the probe displays large blue-shift in UV–vis spectrum and remarkable “turn-on” fluorescence owing to the disruption of intramolecular charge transfer. Meanwhile, the probe also undergoes a naked-eye discernible color change from orange to light pink in the sunlight as well as an obvious fluorescence color change from non-emissive to bright blue under a UV lamp. The detection limit of CN − in aqueous solution can be as low as 20.6   nM, which is much lower than the permissible level of CN − in drinking water according to the WHO. In addition, the probe has been successfully used to determine CN − in real water samples as well as to fabricate test paper kit for CN − detection.

研究领域: 分析化学 · 环境科学
✓ 已验证 DOI PubMed 高影响因子
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SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY · 2025 · IF 4.6

Development of a hemicyanine-based turn-on probe for MAO-A imaging in metabolic disorders in vivo and in serum

Lu Fan,Yulong Jin,Aiguo Zhang,Youzhen Feng,Kai Wang

In this study, A fluorescent/photoacoustic dual-modal probe HD-MAO for hemicyanine derivatives was successfully designed and synthesized, achieving high-sensitivity and high-specificity detection of monoamine oxidase A (MAO-A). Through the ingenious combination of the specific MAO-A recognition group and the hemipanocyanine fluorophore, the probe produced a significant enhancement of the intramolecular charge transfer (ICT) effect after enzymatic digestion, showing the synergistic activation characteristics of fluorescence (∼730 nm) and photoacoustic (∼700 nm) signals, with a detection limit of 0.806 mg/L. In the diet-induced obese mouse model, HD-MAO successfully revealed a significant increase in liver MAO-A activity, which was highly consistent with the serum test results, providing molecular imaging evidence for the early diagnosis of metabolic diseases. The probe behaves stably under physiological conditions and shows no cross-reaction to common interferents. Serum detection experiments further confirm its clinical applicability. This study not only provides an innovative tool for the research on MAO-A-related mechanisms, but also opens up a new approach for the early diagnosis and treatment monitoring of metabolic diseases.

研究领域: 生物成像 · 分子诊断 · 酶检测 · 代谢疾病 · 生物医学光学 · 探针开发
✓ 已验证 DOI PubMed 高影响因子
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MICROCHEMICAL JOURNAL · 2026 · IF 5.2

A reaction-activated near-infrared hemicyanine probe for tandem detection of copper(II) and glutathione in food systems and living cells

Fengjiao Zhou,Qingrui Xu,Ruixin Li,Lihong Leng,Mifang Yang,Xinyu Zhuang,Han Yang,Feng Yang,Xin Wen,Meijuan Zou,Qing Li

Reaction-based fluorescent strategies offer improved selectivity for chemically interrelated analytes but remain underexplored for the sequential detection of Cu 2+ and glutathione (GSH) in complex food and biological systems. Herein, we report a hemicyanine-derived near-infrared probe (HC-TPA) that operates through a Cu 2+ -activated chemical transformation followed by GSH-triggered fluorescence restoration, enabling cascade sensing within a single molecular platform. Coordination of Cu 2+ to the tris(2-pyridyl)methylamine unit induces rapid fluorescence quenching, while subsequent GSH-mediated reaction releases the emissive hemicyanine species, producing distinct near-infrared signals at 668 and 696 nm. The probe responds within 1 min to Cu 2+ and within 20 min to GSH. Quantitative analysis revealed linear detection ranges of 100–800 nM for Cu 2+ and 6–30 μM for GSH, with limits of detection of 48 nM and 0.56 μM, respectively. The reaction-based mechanism affords excellent selectivity and minimizes interference from competing species. Practical applicability was demonstrated through accurate determination of Cu 2+ and GSH in food samples and successful fluorescence imaging in living cells. This work establishes a mechanistically driven tandem sensing strategy for food safety monitoring and bioanalytical applications.

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MOLECULES · 2024 ·Vol. 29 ·期 3 ·618 · IF 4.2

A Coumarin–Hemicyanine Deep Red Dye with a Large Stokes Shift for the Fluorescence Detection and Naked-Eye Recognition of Cyanide

Dongmei Li,Senlin Peng,Xu Zhou,Lingyi Shen,Xianjiong Yang,Hong Xu,Carl Redshaw,Chunlin Zhang,Qilong Zhang

In this study, we synthesized a coumarin–hemicyanine-based deep red fluorescent dye that exhibits an intramolecular charge transfer (ICT). The probe had a large Stokes shift of 287 nm and a large molar absorption coefficient (ε = 7.5 × 105L·mol−1·cm−1) and is best described as a deep red luminescent fluorescent probe withλem= 667 nm. The color of probe W changed significantly when it encountered cyanide ions (CN−). The absorption peak (585 nm) decreased gradually, and the absorption peak (428 nm) increased gradually, so that cyanide (CN−) could be identified by the naked eye. Moreover, an obvious fluorescence change was evident before and after the reaction under irradiation using 365 nm UV light. The maximum emission peak (667 nm) decreased gradually, whilst the emission peak (495 nm) increased gradually, which allowed for the proportional fluorescence detection of cyanide (CN−). Using fluorescence spectrometry, the fluorescent probe W could linearly detect CN−over the concentration range of 1–9 μM (R2= 9913, RSD = 0.534) with a detection limit of 0.24 μM. Using UV-Vis spectrophotometry, the linear detection range for CN−was found to be 1–27 μM (R2= 0.99583, RSD = 0.675) with a detection limit of 0.13 μM. The sensing mechanism was confirmed by1H NMR spectroscopic titrations,13C NMR spectroscopy, X-ray crystallographic analysis and HRMS. The recognition and detection of CN−by probe W was characterized by a rapid response, high selectivity, and high sensitivity. Therefore, this probe provides a convenient, effective and economical method for synthesizing and detecting cyanide efficiently and sensitively.

研究领域: 化学 · 分析化学 · 环境科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ANALYTICAL LETTERS · 2025 · IF 1.8

Development and Application of a Hemicyanine Dye-Based Probe for Real-Time Detection of Aminopeptidase N Activity in Foam Cells and Serum

Yang Xu,Kai Wang,Jian Zhang

Detecting aminopeptidase N (APN) activity in foam cells is crucial for understanding atherosclerosis (AS) progression, but it presents challenges in achieving high specificity and sensitivity to accurately monitor enzyme activity within complex cellular environments. In this investigation, a novel probe, which is specifically targeted at APN and constructed utilizing hemicyanine dyes (HD), has been successfully developed. The probe named AP, in which HD was integrated with APN-specific sequences, exhibited high sensitivity and selectivity when employed in the detection of APN carried out in solution, cellular, and animal models. The probe has undergone significant fluorescence changes upon APN interaction, enabling detection of molecular interactions and enzyme kinetics. Fluorescence analysis showed a linear correlation between fluorescence intensity and APN concentration. In vitro tests confirmed the probe’s specificity without interference from other agents. The probe has detected APN activity in RAW264.7-derived foam cells and monitored serum APN in ApoE−/− mouse models of AS. Cytotoxicity studies showed low toxicity, supporting its biocompatibility. These findings suggest that AP is a promising tool for studying APN-related processes and advancing clinical diagnostics and tissue imaging.

研究领域: 生物化学 · 分子生物学 · 细胞生物学 · 医学诊断 · 生物医学成像
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