Chen Zikang, Zhou Yongjie, Li Li, Ma Wen, Li Yuzhen, Yang Zhen
Department of Pharmacy, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518000, China.
Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Small. 2025 Feb;21(6):e2411787. doi: 10.1002/smll.202411787. Epub 2024 Dec 20.
The second near-infrared window (NIR-II) fluorescence imaging has been widely adopted in basic scientific research and preclinical applications due to its exceptional spatiotemporal resolution and deep tissue penetration. Among the various fluorescent agents, organic small-molecule fluorophores are considered the most promising candidates for clinical translation, owing to their well-defined chemical structures, tunable optical properties, and excellent biocompatibility. However, many currently available NIR-II fluorophores exhibit an "always-on" fluorescence signal, which leads to background noise and compromises diagnostic accuracy during disease detection. Developing NIR-II activatable organic small-molecule fluorescent probes (AOSFPs) for accurately reporting pathological changes is key to advancing NIR-II fluorescence imaging toward clinical application. This review summarizes the rational design strategies for NIR-II AOSFPs based on four core structures (cyanine, hemicyanine, xanthene, and BODIPY). These NIR-II AOSFPs hold substantial potential for clinical translation. Furthermore, the recent advances in NIR-II AOSFPs for NIR-II bioimaging are comprehensively reviewed, offering clear guidance and direction for their further development. Finally, the prospective efforts to advance NIR-II AOSFPs for clinical applications are outlined.
由于具有出色的时空分辨率和深层组织穿透能力，第二近红外窗口（NIR-II）荧光成像已在基础科学研究和临床前应用中得到广泛应用。在各种荧光剂中，有机小分子荧光团因其明确的化学结构、可调的光学性质和出色的生物相容性，被认为是临床转化最有前景的候选者。然而，许多目前可用的NIR-II荧光团表现出“始终开启”的荧光信号，这会导致背景噪声，并在疾病检测过程中影响诊断准确性。开发用于准确报告病理变化的NIR-II可激活有机小分子荧光探针（AOSFP）是推动NIR-II荧光成像走向临床应用的关键。本综述总结了基于四种核心结构（花菁、半花菁、呫吨和BODIPY）的NIR-II AOSFP的合理设计策略。这些NIR-II AOSFP具有很大的临床转化潜力。此外，还全面综述了用于NIR-II生物成像的NIR-II AOSFP的最新进展，为其进一步发展提供了明确的指导和方向。最后，概述了推进NIR-II AOSFP用于临床应用的前瞻性努力。
