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DOI: https://doi.org/10.6023/cjoc202503034

非典型核酸结构的荧光点亮成像检测

  • 陈冰燕 ,
  • 孙洁 ,
  • 熊玲红 ,
  • 何学文
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  • a仿生界面材料科学全国重点实验室 苏州市健康化学与分子诊断重点实验室 苏州大学材料与化学化工学部 苏州 215123;
    b苏州大学苏州医学院公共卫生学院 苏州 215123

收稿日期: 2025-03-31

  修回日期: 2025-05-23

  网络出版日期: 2025-09-25

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Fluorescence Light-up Detection and Imaging of Atypical Nucleic Acid Structures

  • Bingyan Chen ,
  • Jie Sun ,
  • Ling-Hong Xiong ,
  • Xuewen He
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  • aState Key Laboratory of Bioinspired Interfacial Materials Science, The Key Lab of Health Chemistry and Molecular Diagnosis of Suzhou, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China;
    bSchool of Public Health, Suzhou Medical College of Soochow University, Soochow University, Suzhou 215123, China

Received date: 2025-03-31

  Revised date: 2025-05-23

  Online published: 2025-09-25

Supported by

National Natural Science Foundation of China (22274106), the Program of Suzhou Innovation and Entrepreneurship Leading Talents (ZXL2022513) and startup funds from Soochow University.

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摘要

相比于经典的单链和双链型经典核酸结构,非典型核酸结构（如G4s、i-motif、Triplex及环形核酸）因其被发现的重要生物功能和在生理环境下的动态平衡异常与多种重大疾病的密切关联性而逐渐成为生物医学研究的热点。传统凝胶电泳、核磁共振、圆二色性检测技术存在空间分辨率低、破坏性大、缺乏实时动态监测能力等不足。近年来,荧光探针材料因其高灵敏度、快速响应性以及动态实时观测性能等逐渐成为非经典核酸结构检测的前沿工具。本文综述了非经典核酸结构的荧光点亮材料,包括传统荧光小分子、聚集诱导发光原（AIEgens）等,并详述了设计原理、检测机制及应用场景。当前探针技术通过优化分子构效关系提升识别性与信噪比,但仍面临选择性不足、活体穿透性差等挑战。未来需融合多模态成像、人工智能辅助设计及靶向递送系统,构建高灵敏、多通道响应的检测平台,以解析核酸动态构象与疾病关联性,推动开发精准诊断与新型治疗策略。

关键词： 非典型核酸结构; G-四聚体（G4s）; 荧光探针; 选择性识别; 高灵敏; 聚集诱导发光（AIE）; 精准医疗

本文引用格式

陈冰燕 , 孙洁 , 熊玲红 , 何学文 . 非典型核酸结构的荧光点亮成像检测[J]. 有机化学, 0 : 202503034 -202503034 . DOI: 10.6023/cjoc202503034

Abstract

Compared to the single-stranded and double-stranded types of classical nucleic acid structures, atypical nucleic acid structures (such as G4s, i-motif, Triplex, and cyclic nucleic acids) are gradually becoming hotspots in biomedical research due to their important biological functions and the close correlation between their abnormal dynamics equilibrium in physiological environments and a variety of hard-tackle diseases. The traditional gel electrophoresis, nuclear magnetic resonance, and circular dichroism detection techniques have shortcomings such as low spatial resolution, high destructiveness, and lack of real-time dynamic monitoring capability. In recent years, fluorescence imaging has gradually become a cutting-edge tool for non-classical nucleic acid structure detection due to their high sensitivity, fast response and dynamic real-time observation performance. In this contribution, we review the fluorescence materials for lighting-up imaging of non-classical nucleic acid structures, including traditional fluorescent small molecules and aggregation-induced emission luminogens (AIEgens), and detail the design principles, detection mechanisms and application scenarios. Current fluorescence probes have already improved qualities in recognition targetability and signal-to-noise ratio by tuning and optimizing molecular structure-properties relationships, but still faces challenges such as insufficient selectivity and poor penetration capability in vivo. In the future, it is necessary to integrate multimodal imaging, artificial intelligence-assisted design and targeted delivery system to build a highly sensitive and multi-channel responsive platform to thoroughly disclose the association between the dynamic conformation of nucleic acid and disease, and to promote the development of precise and novel therapeutic strategies.

Key words： atypical nucleic acid structure; G-quadruplexes (G4s); fluorescence probe; selective recognition; high sensitivity; aggregation-induced emission (AIE); precise medicine

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