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ANALYTICAL AND BIOANALYTICAL CHEMISTRY · 2026 · IF 4.1

Developing COX-2-targeted fluorescent probes for HClO/ONOO⁻ detection in cancer cells: an integrated experimental and computational study

Zhang Yonglin,Liu Jianxi,Song Shengfa,Hu Jiale,Chen Shulin,Zhu Lulu,Shen Li,Jiang Hao,Xia Yunqing,Yi Xuexue,Yue Ningning,Xue Ying,Liu Wanhui,Zhu Yanping,Xu Lixiao

Overexpression of cyclooxygenase-2 (COX-2) and associated reactive species, specifically hypochlorous acid (HClO) and peroxynitrite (ONOO⁻), in the tumor microenvironment are critical hallmarks for early cancer diagnosis. In this work, we designed and synthesized two fluorescent probes,  S1  and  S2 , for the targeted imaging of HClO and ONOO⁻, respectively. Both probes integrate a celecoxib ligand for COX-2 targeting with a naphthalimide fluorophore. The probes operate via a photoinduced electron transfer (PET) mechanism, producing a distinct fluorescence turn-on response with excellent linearity against analyte concentration ( R 2  = 0.9902 for  S1  with HClO;  R 2  = 0.9897 for  S2  with ONOO⁻). This mechanism was theoretically validated through DFT calculations. In vitro cellular imaging demonstrated that both probes exhibit low cytotoxicity and achieve superior tumor cell selectivity, showing significantly higher fluorescence intensity in COX-2 overexpressing MCF-7 cancer cells than in normal HUVEC cells. The molecular basis for targeting was rigorously investigated using molecular docking and 100 ns molecular dynamics simulations. MM/PBSA calculations revealed favorable binding enthalpies for both  S1  (−80.05 ± 7.19 kcal/mol) and  S2  (−83.76 ± 3.88 kcal/mol) with COX-2, confirming stable and specific complex formation. This integrated experimental and computational strategy yields highly sensitive and selective probes, positioning  S1  and  S2  as promising tools for studying cancer-related biomarkers at the cellular level. Graphical

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Advanced Healthcare Materials · 2025 · IF 9.6

Visualizing GSH-ONOO− Redox and Tracking Lesion-Remedy of Acute Kidney Oxidative Injury Based on a Dual-Site Chemosensor

Meili Yang,Zuzhe Kang,Xinpei Zhong,Sirui Bai,Dong-En Wang,Qin Tu,Sheng Chen,Jinyi Wang,Mao-Sen Yuan

Drug-induced acute kidney injury (DIAKI) is strongly associated with the accumulation of peroxynitrite (ONOO − ) and the depletion of glutathione (GSH), both of which contribute to increased morbidity and mortality. Owing to the lack of an effective method for the real-time monitoring of nephrotoxicity, it remains a diagnostic and therapeutic challenge and is considered a significant issue in clinical practice. Herein, a dual-site fluorescent chemosensor, BPS is developed , which enables the simultaneous real-time monitoring of ONOO − and GSH through distinct channels (ONOO − : λ ex = 410 nm, λ em = 548 nm; GSH: λ ex = 490 nm, λ em = 660 nm) without spectral crosstalk. The sensor displays remarkable sensitivity toward ONOO − and GSH, with low detection limits (181 n m and 2.42 µ m , respectively), exceptional specificity, and anti-interference effects. BPS is used to monitor ONOO − /GSH in real time to track the lesion of cisplatin-stimulated DIAKI and the following remedy process in mice and HK-2 cells for the first time. BPS provides a feasible tool for investigating oxidative stress-related DIAKI disease processes and further exploring some physiological mechanisms. Moreover, this study also offers a strategy for visualizing, modulating, and controlling the intracellular GSH/ONOO − redox.

研究领域: 医学 · 生物化学
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DYES AND PIGMENTS · 2023 · IF 4.5

Development of highly selective novel fluorescence turn-on probe based on carbon dots for sensing peroxynitrite (ONOO−) in vitro and in vivo

Ahmed Mohammed Ali Abdulkhaleq,Yixu Zhao,Kun Qian,Xueshi Wang,Zhongfu Zuo,Xibin Zhou

Peroxynitrite (ONOO − ), a highly reactive nitrogen and oxygen species (RNS/ROS), has been associated with a numerous of pathophysiological diseases, including inflammation, cancer, neurodegenerative, and cardiovascular diseases. There are great demands to develop strategies that can detect ONOO − in biological systems. Herein, we developed a novel fluorescent probe based on carbon dots (CDs) for a very sensitive and selective detection and imaging of endogenous and exogenous ONOO − in cells and animal models. Green light-emitting (527 nm) CDs with high quantum yield (QY) was synthesized by hydrothermal method using resorcinol as carbon source. After the phenolic hydroxyl groups of the CDs are combined with the recognition group of ONOO − via covalent ether bond, the fluorescence is quenched and forming the fluorescent probe. Upon the addition of ONOO − to the probe, the ether bond has broken and the CDs fluorescence has recovered. This response has been detailed investigated, including response time, pH values, selectivity and sensitivity, and linearity range, which confirmed the satisfactory detection ability for ONOO − . The probe shows low cytotoxicity and was successfully applied for imaging of ONOO − exogenously and endogenously in cells and in live models of zebrafish and mice.

研究领域: 生物化学 · 医学 · 材料科学
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NEW JOURNAL OF CHEMISTRY · 2019 ·Vol. 44 ·期 1 ·162-170 · IF 3.069

Peroxynitrite (ONOO−) generation from the HA-TPP@NORM nanoparticles based on synergistic interactions between nitric oxide and photodynamic therapies for elevating anticancer efficiency

Dawei Jiang,Tao Yue,Guichen Wang,Chaochao Wang,Chao Chen,Hongliang Cao,Yun Gao

Due to biological safety and negligible toxicity, nitric oxide (NO) therapy has gained increasing interest in the field of cancer therapy during the past few years. However, individual NO cancer therapy normally exhibited limited therapeutic efficiency. In order to acquire satisfactory therapeutic outcomes, the NO therapy is usually combined with other therapeutic treatments, mostly chemotherapy. Herein, we constructed HA-TPP@NORM nanoparticles based on the co-assembly of an NO donor (NORM) and tetraphenylporphyrin (TPP)-modified hyaluronic acid, which can efficiently generate a highly biocidal molecule of peroxynitrite (ONOO−) via the synergistic interactions of the nitric oxide (NO) therapy and photodynamic therapy (PDT) to enhance the cancer therapeutic efficiency. In addition, MTT results exhibited that without light irradiation, the HA-TPP@NORM nanoparticles have favourable biocompatibility with the cell viability above 95% at the maximum TPP concentration (20 μg mL−1). Under simultaneous irradiation with 365 nm and 650 nm light, ONOO− can be efficiently produced in cancer cells via the direct coupling reaction of the generated NO and superoxide anion radical (O2˙−), which significantly enhanced the anticancer effect, when compared with individual NO therapy or PDT therapy. Therefore, the HA-TPP@NORM nanoparticles may provide a new insight into the design of efficiently NO-related cancer therapeutic systems.

研究领域: 生物医学工程 · 癌症治疗研究
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Journal of Materials Chemistry B · 2020 ·Vol. 8 ·期 11 ·2321-2330 · IF 5.344

Carbon dot targeting to nitrogen signaling molecules for inhibiting neuronal death

Lufei Ouyang,Xiaoyu Mu,Junying Wang,Qifeng Li,Yalong Gao,Haile Liu,Si Sun,Qinjuan Ren,Ruijuan Yan,Jingya Wang,Qiang Liu,Yuanming Sun,Changlong Liu,Hua He,Wei Long,Xiao-Dong Zhang

Free radical-induced oxidative damage and nitrosative stress have been identified as key factors in neuroinflammation responses after traumatic brain injury (TBI), with which reactive oxygen and nitrogen species (RONS), especially nitrogen signaling molecules, are strongly associated. Here, we prepared ultrasmall carbon dot (CD) by using a simple and facile method. In vitro assessment experiments show that the antioxidative CD exhibits an ultrahigh target-scavenging effect for nitrogen signaling molecules, especially the highly reactive ˙NO and ONOO−. However, CD can only partially eliminate conventional oxygen radials such as O2˙− and ˙OH, indicating CD has a preference for RNS modulation. Moreover, in vitro cell experiments and in vivo mice experiments reveal that CD can reduce the reactive oxygen species (ROS) level and lipid peroxidation, enhance superoxide dismutase (SOD) activity and GSSG level, and further improve the survival rate of neuron cells and TBI mice. These results declare that antioxidative CD could serve as an effective therapeutic for TBI.

研究领域: 神经科学 · 药理学 · 材料科学
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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2023 · IF 9.9

Constructing multifunctional Cu Single-Atom nanozyme for synergistic nanocatalytic Therapy-Mediated Multidrug-Resistant bacteria infected wound healing

Xiaochen Qiu,Liang Zhuang,Jian Yuan,Huizhen Wang,Xiaoyu Dong,Shan He,Shanyue Guan,Zhiyue Chang,Pengtao Bao

Developing an effective strategy to combat multi-drug-resistant (MDR) bacteria and promote wound healing without overuse of antibiotics remains an important and challenging goal. Herein, we established a synergistic reactive oxygen species (ROS) and reactive nitrogen species (RNS)-mediated nanocatalytic therapy, which was consisted of a multifunctional Cu single-atom nanozyme loaded with the l -arginine ( l -Arg@Cu-SAzymes) and a low level of hydrogen peroxide (H 2 O 2 ) as a trigger. l -Arg@Cu-SAzymes can possess excellent dual enzyme-like activities: catalase (CAT)-like activity that decompose H 2 O 2 into O 2 , and subsequent oxidase (OXD)-like activity that convert O 2 to cytotoxic superoxide anion radical (•O 2 − ). Meanwhile, l -Arg@Cu-SAzymes can also be triggered by H 2 O 2 to release nitric oxide (NO), which can continue to react with •O 2 – to generate more lethal peroxynitrite (ONOO − ). Collectively, the synergistic ROS and RNS mediated by l -Arg@Cu-SAzymes endow the treatment system with an outstanding antibacterial ability against MDR bacteria and reduce the inflammation at the wound site. Furthermore, l -Arg@Cu-SAzymes-mediated NO and O 2 release promote the cell proliferation , collagen synthesis, and the angiogenesis , as well as facilitate macrophage polarization to reparative M2 phenotype, thereby accelerating wound closure and tissue remodeling. Therefore, l -Arg@Cu-SAzymes-based synergistic nanocatalytic therapy can be regarded as a promising strategy for MDR bacterial infected wounds treatment, owing to their potent antibacterial efficacy and enhanced tissue remodeling effects.

CAS / MDL: 74-79-3
研究领域: 纳米技术 · 生物材料 · 生物医学工程 · 微生物学 · 伤口愈合
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Advanced Science · 2024 · IF 14.3

Zwitterion-Lubricated Hydrogel Microspheres Encapsulated with Metformin Ameliorate Age-Associated Osteoarthritis

Jiahui Hou,Yanpeng Lin,Chencheng Zhu,Yupeng Chen,Rongmin Lin,Hancheng Lin,Dahai Liu,Daogang Guan,Bin Yu,Jun Wang,Hangtian Wu,Zhuang Cui

Chondrocyte senescence and reduced lubrication play pivotal roles in the pathogenesis of age-related osteoarthritis (OA). In the present study, highly lubricated and drug-loaded hydrogel microspheres are designed and fabricated through the radical polymerization of sulfobetaine (SB)-modified hyaluronic acid methacrylate using microfluidic technology. The copolymer contains a large number of SB and carboxyl groups that can provide a high degree of lubrication through hydration and form electrostatic loading interactions with metformin (Met@SBHA), producing a high drug load for anti-chondrocyte senescence. Mechanical, tribological, and drug release analyses demonstrated enhanced lubricative properties and prolonged drug dissemination of the Met@SBHA microspheres. RNA sequencing (RNA-seq) analysis, network pharmacology, and in vitro assays revealed the extraordinary capacity of Met@SBHA to combat chondrocyte senescence. Additionally, inducible nitric oxide synthase (iNOS) has been identified as a promising protein modulated by Met in senescent chondrocytes, thereby exerting a significant influence on the iNOS/ONOO-/P53 pathway. Notably, the intra-articular administration of Met@SBHA in aged mice ameliorated cartilage senescence and OA pathogenesis. Based on the findings of this study, Met@SBHA emerges as an innovative and promising strategy in tackling age-related OA serving the dual function of enhancing joint lubrication and mitigating cartilage senescence.

研究领域: 生物医学工程 · 药学 · 风湿病学 · 老年学 · 分子生物学
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ADVANCED MATERIALS · 2023 · IF 29.4

“Ice & Fire” Supramolecular Cell-Conjugation Drug Delivery Platform for Deep Tumor Ablation and Boosted Anti-Tumor Immunity

Meng Xu,Haidong Zha,Jiamao Chen,Simon Ming-Yuen Lee,Qi Wang,Ruibing Wang,Ying Zheng

Cancer recurrence and metastasis are two major challenges in the current clinical therapy. Here, we synthesized a novel diketopyrrolopyrrole-based photothermal reagent (DCN) with unique J-aggregation-induced redshift to achieve efficient tumor thermal ablation under safe power (0.33 W/cm 2 ). Meanwhile, S-nitroso-N-acetylpenicillamine (SNAP) was co-loaded with near-infrared (NIR)-absorbing DCN in amphiphilic polymers to realize heat-induced massive release of nitric oxide (NO), which could form oxidant peroxynitrite (ONOO – ) to active MMPs, thereby degrading the compact tumor extracellular matrix (ECM) to improve the ablation depth and infiltration of immune cells. Through a facile supramolecular assembly method, the DCN/SNAP nanoparticles were anchored to liquid nitrogen-frozen cancer cells (LNF), achieving enhanced anti-tumor immune responses and effective inhibition of distant tumor and pulmonary metastases after only one treatment. The safety and effectiveness of this supramolecular cell-conjugation platform were verified by 2D/3D cellular experiments and bilateral tumor model, confirming the thermal ablation-gas permeation-antigen presentation therapeutic mode had promising anticancer prospects. This article is protected by copyright. All rights reserved

CAS / MDL: 41085-99-8 210892-23-2
研究领域: 肿瘤学 · 药学 · 生物医学工程 · 免疫疗法
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