化学学报 ›› 2025, Vol. 83 ›› Issue (10): 1252-1266.DOI: 10.6023/A25050200 上一篇    下一篇

综述

用于神经递质检测与生物成像的有机小分子荧光探针

孟倩a, 张琪伟a,b,*()   

  1. a 华东师范大学化学与分子工程学院 上海市绿色化学与化工过程绿色化重点实验室 上海 200241
    b 华东师范大学 医学磁共振与分子影像技术研究院 上海 200241
  • 投稿日期:2025-05-31 发布日期:2025-08-12
  • 通讯作者: 张琪伟
  • 作者简介:

    孟倩, 2024年毕业于阜阳师范大学, 获硕士学位. 现为华东师范大学博士研究生, 导师为张琪伟教授. 主要从事有机发光材料的设计合成及其分析与成像应用研究.

    张琪伟, 华东师范大学化学与分子工程学院教授、博士生导师, 国家自然科学基金优秀青年科学基金获得者. 2005~2014年在华东理工大学获得学士与博士学位, 师从田禾院士. 2014~2018年, 先后在荷兰奈梅亨大学(Radboud University, 合作导师Roeland J.M. Nolte院士)和美国圣母大学(University of Notre Dame, 合作导师Bradley D. Smith教授)从事博士后研究. 2018年回国入职华东师范大学, 主要从事有机光功能材料、荧光传感与生物成像和光学诊疗等领域的研究.

    “中国青年化学家”专辑.

  • 基金资助:
    国家自然科学基金(22322405); 国家自然科学基金(22274055); 上海市基础研究特区计划(TQ20240206)

Organic Small-Molecule Fluorescent Probes for Neurotransmitter Sensing and Bioimaging

Qian Menga, Qiwei Zhanga,b,*()   

  1. a Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200241
    b Institute of Magnetic Resonance and Molecular Imaging in Medicine, East China Normal University, Shanghai 200241
  • Received:2025-05-31 Published:2025-08-12
  • Contact: Qiwei Zhang
  • About author:

    For the VSI “Rising Stars in Chemistry”.

  • Supported by:
    National Natural Science Foundation of China(22322405); National Natural Science Foundation of China(22274055); Shanghai Pilot Program for Basic Research(TQ20240206)

神经递质作为介导神经元间信息传递、调控神经环路及维持脑功能稳态的关键信使分子, 其动态监测对解析神经生理/病理机制具有重要意义. 有机小分子荧光探针以其优异的结构稳定性、生物相容性、识别机制的可设计性, 以及发光特性的灵活可调性, 为神经递质的检测和成像提供了理想的方式. 此文从有机小分子荧光探针的分子设计策略、共价/非共价识别原理、信号转导机制, 以及生物成像性能等方面出发, 对神经递质荧光探针的最新研究进展进行综述. 在此基础上, 对当前探针的局限性进行了深入分析, 并对未来新型探针的设计方向进行了展望, 旨在为新一代高性能神经化学探针的研发提供理论框架与路线图, 以促进神经科学和临床诊断技术的发展.

关键词: 荧光探针, 神经递质, 有机小分子, 超分子, 生物成像

Neurotransmitters are essential mediators of neuronal communication, governing neural circuit plasticity and maintaining cerebral functional homeostasis. They can be classified into major categories including monoamines, amino acids, acetylcholine, neuropeptides, purines, gaseous neurotransmitters, etc. Deciphering the dynamic fluctuations in neurotransmitter concentrations and distributions is paramount for elucidating fundamental neurophysiological processes and unraveling the mechanisms underpinning neuropathological conditions, such as Alzheimer's disease, Parkinson's disease, depression, etc. Fluorescence imaging technique employs specific probes that transduce the biochemical event of neurotransmitter recognition into a quantifiable optical signal, enabling non-invasive, highly specific visualization with high spatiotemporal resolution in live systems, representing an exceptionally promising class of tools for neurotransmitter detection. Owing to the compact size, excellent structural stability, high biocompatibility, tunable photophysical properties, and designable recognition mechanisms, organic small-molecule fluorescent probes act as ideal candidates for sensitive and selective neurochemical imaging. This review examines the advancements in the development and application of organic fluorescent probes for neurotransmitter detection, focusing on molecular designs, recognition principles (covalent or non-covalent interactions), signal transduction mechanisms (e.g., photoinduced electron transfer, intramolecular charge transfer, fluorescence resonance energy transfer), analytical performance, and their imaging capabilities in live cells, tissues, and in vivo models. A dedicated section provides a critical analysis of the prevailing limitations hindering broader application of current organic small-molecule fluorescent probes, such as challenges with reversibility, slow response times, photobleaching, limited multiplexing capability, insufficient blood-brain barrier penetration, and depth limitations in in vivo imaging. Building upon this assessment, we offer forward-looking perspectives on the future trajectory of fluorescent probe development. Key focus areas include engineering probes with enhanced binding kinetics and reversibility for real-time monitoring, superior photostability for longitudinal studies, capabilities for multiplexed analysis, ideal excitation/emission properties for deeper tissue penetration, and improved pharmacokinetic properties for efficient BBB crossing. This review aims to provide strategic design insights and a developmental roadmap for the next generation of high-performance neurochemical probes, thereby advancing fundamental neuroscience research and clinical diagnostic technologies.

Key words: fluorescent probes, neurotransmitters, organic small molecules, supermolecules, bioimaging