A mitochondrial targeted fluorescent probe for imaging nitroreductase activity and photodynamic therapy in tumor cells

IF 5.6 1区化学 Q1 CHEMISTRY, ANALYTICAL

Talanta Pub Date : 2024-12-18 DOI:10.1016/j.talanta.2024.127392

Ya-Ting Bao , Hai-Bo Mao , Ke-Wei Lei , Jing-Bo Hu , Jing Huang

{"title":"A mitochondrial targeted fluorescent probe for imaging nitroreductase activity and photodynamic therapy in tumor cells","authors":"Ya-Ting Bao , Hai-Bo Mao , Ke-Wei Lei , Jing-Bo Hu , Jing Huang","doi":"10.1016/j.talanta.2024.127392","DOIUrl":null,"url":null,"abstract":"<div><div>The hypoxic environment in tumors is closely linked to tumor structure, function, dissemination, invasion, metastasis, and drug resistance. Nitroreductase (NTR) is often recognized as a biomarker to evaluate the hypoxia degree for tumor cells. Traditional detection methods such as PET, MRI and multispectral photoacoustic tomography have limitations. Fluorescent probes have garnered attention due to their high sensitivity, rapid response, specificity, and non-invasive nature. In this study, we introduced a novel small molecule fluorescent probe, T-TPE-NO<sub>2</sub>, designed with an AIE molecular framework TPE and successfully targeted to the mitochondria of tumor cells. The probe had high selectivity and could detect NTR activity in a broad pH range. Additionally, the probe exhibits high sensitivity with a LOD of 46.3 ng/mL. Under tumor NTR, the probe emitted strong fluorescence signals and generated a substantial amount of reactive oxygen species upon laser irradiation, thereby inducing tumor cell death and enabling photodynamic therapy. The synthesis, structural and morphological characterization of the probe were rigorously validated. Experimental results demonstrate that T-TPE-NO<sub>2</sub> exhibited high sensitivity and selectivity for tumor cells, highlighting its potential application in photodynamic therapy. This research offers a new approach for the detection and treatment of tumor hypoxia.</div></div>","PeriodicalId":435,"journal":{"name":"Talanta","volume":"285 ","pages":"Article 127392"},"PeriodicalIF":5.6000,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Talanta","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0039914024017740","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ANALYTICAL","Score":null,"Total":0}

引用次数: 0

Abstract

The hypoxic environment in tumors is closely linked to tumor structure, function, dissemination, invasion, metastasis, and drug resistance. Nitroreductase (NTR) is often recognized as a biomarker to evaluate the hypoxia degree for tumor cells. Traditional detection methods such as PET, MRI and multispectral photoacoustic tomography have limitations. Fluorescent probes have garnered attention due to their high sensitivity, rapid response, specificity, and non-invasive nature. In this study, we introduced a novel small molecule fluorescent probe, T-TPE-NO₂, designed with an AIE molecular framework TPE and successfully targeted to the mitochondria of tumor cells. The probe had high selectivity and could detect NTR activity in a broad pH range. Additionally, the probe exhibits high sensitivity with a LOD of 46.3 ng/mL. Under tumor NTR, the probe emitted strong fluorescence signals and generated a substantial amount of reactive oxygen species upon laser irradiation, thereby inducing tumor cell death and enabling photodynamic therapy. The synthesis, structural and morphological characterization of the probe were rigorously validated. Experimental results demonstrate that T-TPE-NO₂ exhibited high sensitivity and selectivity for tumor cells, highlighting its potential application in photodynamic therapy. This research offers a new approach for the detection and treatment of tumor hypoxia.

Abstract Image

查看原文本刊更多论文

线粒体靶向荧光探针，用于成像硝基还原酶活性和肿瘤细胞中的光动力疗法。

肿瘤缺氧环境与肿瘤的结构、功能、传播、侵袭、转移、耐药等密切相关。硝基还原酶（Nitroreductase， NTR）常被认为是评估肿瘤细胞缺氧程度的生物标志物。传统的检测方法如PET、MRI和多光谱光声断层扫描都有局限性。荧光探针因其高灵敏度、快速反应、特异性和非侵入性而备受关注。在本研究中，我们引入了一种新型的小分子荧光探针T-TPE-NO2，该探针采用AIE分子框架TPE设计，成功靶向肿瘤细胞的线粒体。该探针具有高选择性，可在较宽的pH范围内检测NTR活性。此外，探针具有高灵敏度，LOD为46.3 ng/mL。在肿瘤NTR下，探针在激光照射下发出强烈的荧光信号，产生大量的活性氧，从而诱导肿瘤细胞死亡，实现光动力治疗。对探针的合成、结构和形态特征进行了严格的验证。实验结果表明，T-TPE-NO2对肿瘤细胞具有较高的敏感性和选择性，在光动力治疗中具有潜在的应用前景。本研究为肿瘤缺氧的检测和治疗提供了新的途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Talanta 化学-分析化学

CiteScore

12.30

自引率

4.90%

发文量

861

审稿时长

29 days

期刊介绍： Talanta provides a forum for the publication of original research papers, short communications, and critical reviews in all branches of pure and applied analytical chemistry. Papers are evaluated based on established guidelines, including the fundamental nature of the study, scientific novelty, substantial improvement or advantage over existing technology or methods, and demonstrated analytical applicability. Original research papers on fundamental studies, and on novel sensor and instrumentation developments, are encouraged. Novel or improved applications in areas such as clinical and biological chemistry, environmental analysis, geochemistry, materials science and engineering, and analytical platforms for omics development are welcome. Analytical performance of methods should be determined, including interference and matrix effects, and methods should be validated by comparison with a standard method, or analysis of a certified reference material. Simple spiking recoveries may not be sufficient. The developed method should especially comprise information on selectivity, sensitivity, detection limits, accuracy, and reliability. However, applying official validation or robustness studies to a routine method or technique does not necessarily constitute novelty. Proper statistical treatment of the data should be provided. Relevant literature should be cited, including related publications by the authors, and authors should discuss how their proposed methodology compares with previously reported methods.