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ONOO−
TALANTA · 2025 · IF 6.1

A KIM-1 Targeted ONOO−-Sensitive NIR Fluorescence Probe for Enhanced Acute Kidney Injury Diagnosis

Mengyu Du,Fangfang Sun,Yilin Sun,Zhenzhen Ma,Chenshuo Wang,Mengyu Liu,Ling Zhu,Hanchun Yao

Acute kidney injury (AKI) is a swiftly advancing condition that may result in kidney failure and pose a significant threat to life. Therefore, diagnosis of AKI is crucial for treating AKI and preventing the worsening of the condition. We developed a near-infrared fluorescent probe, CyO@CD-Ser, designed for the diagnosis of AKI. This probe targets kidney injury molecule-1 (KIM-1) and is activated by ONOO − . It consists of L-serine-modified β-cyclodextrin and compound CyO. In this system, ONOO − , a novel biomarker for AKI, triggers the oxidation of CyO to produce compound CyOH, resulting in a pronounced enhancement of near infrared fluorescence, offering a clear, visual signal for the detection of AKI. Through its modification with L-serine, β-cyclodextrin is able to efficiently penetrate cells by targeting KIM-1 receptors, thereby enhancing its specificity and effectiveness. In vitro and in vivo experiments demonstrate the probe's high sensitivity and biocompatibility, with a detection limit of 42.7 nM for ONOO − . Fluorescence is detectable in cisplatin-induced AKI after 12 hours, becoming significant at 24 hours. This suggests that CyO@CD-Ser can identify AKI earlier than traditional methods, offering a valuable tool for studying and diagnosing drug-induced AKI. Consequently, the probes we constructed can detect AKI early by precisely targeting and identifying biomarkers, preventing the deterioration of the condition, and providing an opportunity for early treatment for patients.

研究领域: 医学诊断 · 生物成像 · 分子探针 · 肾脏病学 · 荧光传感器 · 药物毒理学
✓ 已验证 DOI PubMed 高影响因子
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SENSORS AND ACTUATORS B-CHEMICAL · 2024 · IF 8

Bifunctional mitochondria-targeting fluorescence probe for in vivo ONOO− and viscosity sensing without signal crosstalk

Qian Chen,Lin Shen,Jia-Lin Cui,Xiao-Hui Liu,Han-Yang Zou,Xiao-Qun Cao,Shi-Li Shen,Xiao-Fan Zhang

Viscosity is an important mitochondrial micro-environmental parameter, and peroxynitrite (ONOO − ) is one type of reactive oxygen species (ROS), both of which play critical roles in cellular activities. Abnormalities in mitochondrial viscosity or aberrant concentration of ONOO − can lead to mitochondrial dysfunctions and diseases. Here, by incorporating different substituents into the xanthene core, we develop three molecular probes P1 , P2 and P3 , all of which are dual-responsive to viscosity and ONOO − . Among P1 - P3 , the probe P2 displays large fluorescence enhancements of 49-fold for viscosity (at 819 nm) and 66-fold for ONOO − (at 511 nm), respectively. More importantly, P2 is capable of detecting viscosity and ONOO − simultaneously via two well-separated channels (λ em = 819/511 nm), which can largely eliminate the influence of fluorescence signal crosstalk. P2 has good specificity for viscosity and ONOO − , as well as brilliant biocompatibility and mitochondria-targeting ability. In addition, P2 can be applied to monitor nystatin and starvation-induced viscosity increase as well as endogenous and exogenous ONOO − alterations in living cells. The probe has been used for in situ fluorescence visualization of viscosity in the inflammatory and diabetic mice. Further, we have realized the simultaneous detection of viscosity and ONOO − during ferroptosis. Hence, P2 might be expected to be applied in researches concerning bifunctional detection of viscosity and ONOO − in some diseases.

研究领域: 生物化学 · 分子生物学 · 细胞生物学 · 生物医学工程 · 药理学
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Redox Biology · 2021 · IF 11.799

A novel fluorescent probe for the detection of peroxynitrite and its application in acute liver injury model

Chen Jin,Pengfei Wu,Yushun Yang,Zhenxiang He,Hailiang Zhu,Zhen Li

Realizing the early diagnosis of acute liver injury has become a hotspot in recent years. Since the current indexes are not specific, developing novel probes with new recognition group remains a necessity. In this work, we developed a novel fluorescent probe, NNP , for the detection of ONOO − in acute liver injury (ALI). The in vitr o evaluation of NNP indicated the advantages including high sensitivity (LOD = 0.13  μ M), rapid response (<25 s), naked-eye (red to yellow), and stability under various pH (4–10) and time (>48 h) conditions. Accordingly, NNP achieved the dose-dependent detection of ONOO − in human hepatic stellate LX-2 cells. Further, in the ALI model mice, NNP could monitor the ONOO − level in the occurrence of ALI in situ (in the liver region) with a steady performance. Subsequent immunohistochemical and imaging studies confirmed that NNP could achieve the detection of endogenous ONOO − in ALI liver tissues. This work introduced a practical implement for the ONOO − detection in ALI as well as a referable example for the establishment of molecular indexes in pre-clinical diagnosis.

研究领域: 生物化学 · 分子生物学 · 医学诊断 · 药理学
✓ 已验证 DOI PubMed 高影响因子
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ACS Applied Bio Materials · 2020 · IF 0

Nanoliposomal Ratiometric Fluorescent Probe toward ONOO– Flux

Jie Zhang,Jianfei Kan,Yanyan Sun,Miae Won,Ji Hyeon Kim,Weifen Zhang,Jin Zhou,Zhaosheng Qian,Jong Seung Kim

Peroxynitrite (ONOO–), a powerful biological oxidant, is produced in the mitochondria and reacts with many biomolecular targets under various pathological conditions, leading to a range of disease states. In this work, we developed a nanoliposome-encapsulated ratiometrically fluorescent probe (NRF) based on a hemicyanine structure Cy-O obtained by facile synthesis. Upon reaction with ONOO–, the oxidation and hydrolysis of a π-conjugation system within the nanoliposome triggers a ratiometrically fluorescent response and a large-scale emission shift (238 nm), which provides a specific and sensitive means for the ONOO– detection. Moreover, we have performed DFT calculation at the 6-31+G(d,p) level using a suite of Gaussian 09 programs to obtain insights into the chemical structure optical properties of Cy-O. In addition, the practical applications of the nanoprobe to image exogenous and endogenous ONOO– were achieved further in live cells and animals triumphantly.

CAS / MDL: 1313-59-3
研究领域: 分析化学 · 生物化学 · 分子生物学 · 材料科学
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SENSORS AND ACTUATORS B-CHEMICAL · 2025 · IF 7.7

A novel fluorescent sensing strategy for point-of-care monitoring of Hg2 +-induced oxidative stress in HeLa cells, zebrafish and mice models

Meiqing Zhu,Manjie Chen,Xinfu Zhu,Xingyu Zhu,Rimao Hua,Xiaofan Yang,Saraschandra Naraginti,Yi Wang

Hg 2+ -induced oxidative stress is an important pathway mediating biotoxicity, and the dynamics of reactive oxygen/nitrogen species (ROS/RNS) is a key indicator for quantitatively assessing the level of oxidative stress. Herein, a novel “targeted dual recognition” NIR fluorescent chemosensor (DDPT) was constructed for the specific recognition of Hg 2+ and ONOO - . The DDPT activated by Hg 2+ for the detection of ONOO - exhibited rapid response (<50 s), high sensitivity (16.8 nM) and excellent selectivity. The P = S bond in DDPT is oxidized to P = O by Hg 2+ , followed by ONOO - the specific attack on the P-O bond to break it, releasing the DDPT-OH to generate a significant fluorescence enhancement (with a Stokes shift up to 188 nm). The response mechanism of DDPT was systematically verified by 1 HNMR, HRMS and DFT theoretical calculations. Furthermore, DDPT was successfully evaluated for imaging Hg 2+ -induced ONOO - dynamics in cellular, zebrafish and mouse models due to its advantages of low cytotoxicity, high tissue permeability and biocompatibility. The results reveal that Hg 2+ induces oxidative stress and increases ONOO - concentration to destroy the antioxidant defense system of organisms, thus triggering the toxic pathway of oxidative stress. The development of DDPT provides a basis for analyzing pollutant-oxidative stress interactions, assessing health risks, and developing targeted intervention strategies.

研究领域: 生物化学 · 毒理学 · 医学影像
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JOURNAL OF MOLECULAR STRUCTURE · 2025 · IF 4.7

A bifunctional AIEgen fluorescent probe for detection viscosity and ONOO- in living cells

Huaqin Jiang,Lingling Shi,Wenxiang Wang,Yang Yang,Min Fang,Weiju Zhu,Cun Li

The peroxynitrite anion (ONOO - ) and viscosity play crucial roles in both physiological and pathological processes. In this study, we developed a bifunctional fluorescent probe MAR with an aggregation-induced emission (AIE) feature for detecting viscosity and ONOO - across different channels. MAR exhibited significant fluorescence enhancement to viscosity with a red emission at 600 nm and a good linear relationship in the range of 11.6 to 956 cP. Additionally, MAR could rapidly recognize and quantitatively respond to ONOO - with high selectivity, good sensitivity, a low detection limit (LOD = 6.97 nM), and a wide range of pH value (4.0 - 10.0), accompanied by visible blue fluorescence emission at 408 nm. The considerable wavelength separation (Δλ = 192 nm) between the maximum emission peaks of MAR for viscosity and ONOO - ensured minimal signal crosstalk in bioimaging. Cell imaging experiments indicated that MAR could target intracellular lipid droplets and respond to the changes of viscosity and ONOO - through independent red and blue channels. These results indicated that the AIEgen fluorescence sensor MAR was a promising candidate for detecting ONOO - levels and viscosity changes in live cells.

CAS / MDL: 56278-50-3
研究领域: 生物化学 · 医学检测 · 材料科学
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ACS Nano · 2021 · IF 15.881

Tumor-Specific ONOO– Nanogenerator for Improved Drug Delivery and Enhanced Chemotherapy of Tumor

Ying Chen,Zi-Hao Li,Pei Pan,Run-Yao Zeng,Xian-Zheng Zhang

Multiple biological barriers in solid tumors severely restrict the penetration of nanomedicines, which is a main cause for therapeutic failure in traditional tumor treatment. Here, a tumor-specific nanogenerator of peroxynitrite (ONOO–), prepared by loading cisplatin and sodium nitroprusside into poly(d,l-lactide-co-glycolide) polymersomes, was designed to improve drug delivery and enhance tumor chemotherapy. After a cascade of nicotinamide adenine dinucleotide phosphate oxidases catalysis and glutathione reduction, the nanogenerator, namely, PMCS, could selectively induce the generation of ONOO– in tumor. The generated ONOO– could not only strengthen vascular permeability significantly but also improve the accumulation and penetration of PMCS in tumor by activating matrix metalloproteinases-mediated degradation of extracellular matrix. Along with endocytosis, PMCS released cisplatin to induce tumor cell apoptosis. Moreover, free cisplatin liberated from dead cells infected neighboring tumor cells quickly via ONOO–-mediated up-regulated copper transporter 1, further amplifying chemotherapeutic efficacy. This study advances ONOO– as a potent modality to address the main issues of therapeutic delivery, including but not limited to chemotherapy.

CAS / MDL: 26780-50-7 210892-23-2
研究领域: 药学 · 肿瘤学 · 生物医学工程
✓ 已验证 产品关联 DOI PubMed 高影响因子
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SENSORS AND ACTUATORS B-CHEMICAL · 2025 · IF 7.7

A FRET-based ratiometric fluorescent chemosensor for mitochondrial ONOO⁻ detection with application to Rheumatoid Arthritis

Jianhong Liu,Xinyue Zhao,Li Zhang,Haowen Zhou,Xudong Li,Guorui Zheng,Xibin Zhou,Yongjin Peng,Jie Zhang

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by progressive joint destruction, where early diagnosis is crucial for impeding disease progression. Peroxynitrite (ONOO⁻), a key reactive nitrogen species, is critically involved in the pathogenesis of RA and represents a promising diagnostic target for early detection. Herein, we developed MRN, a mitochondria-targeting ratiometric fluorescent probe based on a Förster resonance energy transfer (FRET) mechanism for the dynamic monitoring of ONOO⁻ in RA inflammatory models. The probe integrates a rhodamine-naphthalimide FRET pair and a hydrazide group as the specific recognition unit, which facilitates a rapid, ONOO⁻-triggered ratiometric response within 30   seconds and achieves a detection limit of 7.5   nM. Furthermore, the conjugation of a triphenylphosphonium group ensures precise mitochondrial localization. Cellular assays demonstrated excellent biocompatibility and specific mitochondrial targeting. We successfully applied MRN for real-time ratiometric imaging of both endogenous and exogenous ONOO⁻ fluctuations in live BV-2 cells. Importantly, in a Complete Freund's Adjuvant (CFA)-induced rheumatoid arthritis mouse model, MRN enabled in situ ratiometric fluorescence imaging of ONOO⁻ at articular sites, revealing a strong positive correlation between the fluorescence signal intensity and the degree of inflammatory severity. This work establishes MRN as a novel and robust molecular tool for the early diagnosis of RA.

✓ 已验证 产品关联 DOI 高影响因子
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JOURNAL OF FLUORESCENCE · 2025 · IF 3.1

A New Fluorescent Probe based on Carbazole-Benzopyranyl for the Recognition of ONOO− and its Application

Wang Peng,Wang Qian,Tao Yana,Ji Yuan,Fang Min,Li Cun,Zhu Weiju

In this study, we successfully synthesized a colorimetric and photoluminescent fluorescent probe CBB by introducing benzopyran malononitrile at the 3-position of N-butylcarbazole and pinacol borate structure at the 6-position of N-butylcarbazole. The probe CBB characterized by a substantial Stokes shift (146 nm) demonstrates high selectivity and sensitivity to ONOO − . The probe CBB can specifically identify ONOO − by UV–Vis and fluorescence spectroscopic techniques. When ONOO − is added to the solution of CBB, the solution’s color transitions from orange to colorless in daylight, and from pink to blue under a 365 nm UV lamp, making these can be easily recognized by the naked eye. The recognition mechanism was validated using 1 H NMR, mass spectrometry (MS) and density functional theory (DFT) calculations. In addition, cell imaging experiments demonstrated that CBB effectively captured the fluorescence signals in both the red and blue channels of HeLa cells through fluorescence confocal microscopy, successfully identifying exogenous ONOO − within these cells. These results show that the probe CBB possesses strong monitoring capabilities for ONOO − , offering new opportunities for research and application in related fields.

✓ 已验证 DOI PubMed 高影响因子
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DYES AND PIGMENTS · 2025 · IF 4.2

Development of a near-infrared ratiometric fluorescent probe for the detection of ONOO− in ferroptosis model

Guo-Ping Zu,Pingping Xiong,Meng-Chen Pei,Chengjie Wang,Huawei Niu,Hong Chen,Yong Meng

Peroxynitrite (ONOO − ) is closely associated with several pathophysiological events due to its high oxidation and nitrification reactivity, which can cause irreparable damage to a variety of biomolecules when present in excess. Consequently, the development of a reliable ONOO − detection method is essential for understanding its role. Given the significant imaging advantages of ratiometric and near-infrared (NIR) probes, a ratiometric NIR fluorescence probe ( FYS ) was developed for the visual detection of ONOO − both in vitro and in vivo . Probe FYS offers several benefits, including a large fluorescence emission shift (184 nm), a low detection limit (0.75 μM), good selectivity, and rapid detection. Inspired by these outstanding characteristics, it has been successfully utilized for imaging endogenous and exogenous ONOO − in cells. More importantly, this probe could be used to monitor variations in ONOO − levels as ferroptosis progresses. We anticipate that this probe will be widely applied as a potent tool to investigate the biological function of ONOO − , thereby facilitating a deeper understanding of ferroptosis.

CAS / MDL: 108-94-1 1289218-74-1
研究领域: 分析化学 · 生物化学 · 细胞生物学 · 荧光成像 · 氧化应激研究
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ANALYST · 2019 ·Vol. 144 ·期 6 ·2150-2157 · IF 4.019

Real-time monitoring of peroxynitrite (ONOO−) in the rat brain by developing a ratiometric electrochemical biosensor

Feiyue Liu,Hui Dong,Yang Tian

As a reactive oxygen species (ROS), peroxynitrite (ONOO−) generated by nitric oxide (NO) and superoxide anion (O2˙−) plays important roles in physiological and pathological processes in the brain. However, the lack of reliable and durable analytical methods in vivo is still a bottleneck to understanding the signal pathway of ONOO− in the brain. In this work, a ratiometric electrochemical biosensor was developed for real-time monitoring and accurate quantification of ONOO− in the rat brain followed by cerebral ischemia. Firstly, a novel organic molecule, 4-(S-(6-mercaptohexyl)benzothioate-6-yl)-7-(diethylamino)-2-(4-(piperazinyl diferroformamide-1-yl)phenyl)chromenylium (HEMF), with a specific recognition group toward ONOO− and ferrocene as an electroactive group, was designed and synthesized for determination of ONOO− with high selectivity. The oxidation peak of ferrocene decreased with increasing concentration of ONOO−, with a rapid response within 15 s, because the pyrylium group in HEMF molecule specifically reacted with ONOO−, resulting in the loss of the ferrocene group from the HEMF molecule through a ring-opening reaction. Meanwhile, 5′-MB-GGCGCGATTTT-SH-3′ (SH-DNA-MB) was optimized as an inner reference molecule, enabling accurate quantification of ONOO− while avoiding environmental effects. The oxidation peak current ratio between ferrocene and MB demonstrated good linearity with concentrations of ONOO− from 20.0 nM to 2.0 μM. The achieved detection limit was as low as 12.1 ± 0.8 nM. The developed biosensor showed remarkable selectivity against potential interferences in the brain, such as other ROS, metal ions, amino acids and bioactive species, due to the specific reaction between the pyrylium group and ONOO−. As a result, the present ratiometric electrochemical biosensor with significant analytical performance, including high temporal resolution, high selectivity and accuracy, combined with the unique characteristics of carbon fiber microelectrode (CFME), such as high spatial resolution and good biocompatibility, was successfully applied in real-time determination of ONOO− in rat brains followed by global cerebral ischemia.

研究领域: 分析化学 · 神经科学 · 电化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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SENSORS AND ACTUATORS B-CHEMICAL · 2025 · IF 7.7

A Sequentially activated probe for simultaneous fluorescence imaging of ONOO― and HOBr in brain to indicate Alzheimer’s Disease

Hui Wang,Tiancong Xiu,Xiaoting Zhang,Lianhuan Zhu,Haonan Bi,Ping Li,Bo Tang

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder characterized by progressive cognitive decline and memory loss. However, clinical diagnosis is only effective for patients with obvious clinical symptoms, which cannot provide precise diagnosis in the early stages of AD. Therefore, developing a practical tool for rapid and accurate diagnosis of AD is of paramount importance. Research suggests that reactive oxygen species (ROS), specifically peroxynitrite (ONOO ― ) and hypobromous acid (HOBr), may involve in the progression of AD, which could serve as biomarkers. Research on the simultaneous imaging of two kinds of ROS in AD using a single fluorescence probe remains sparse. To enhance diagnostic accuracy, our research designed an ingenious small-molecule fluorescent probe, NBO, for the sequential detection of ONOO ― and HOBr with distinguishable spectra. By utilization of NBO, elevated ONOO ― and HOBr levels were found in AD brain, and the therapeutic efficacy of AD drugs were successfully assessed.

研究领域: 神经生物学 · 医学影像学 · 生物化学
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