广西师范大学陈华团队近日研究了生物体内可控原位合成NIR-II半花青碱用于高效肿瘤成像。2025年6月24日出版的《中国化学》杂志发表了这项成果。

第二近红外区（NIR-II）小分子荧光团由于其明确的化学结构、优越的代谢特性、深入组织渗透和前所未有的清晰度，在生物医学成像方面具有很大的前景。然而，由于需要高温、强酸或强碱和无水条件，不可能应用传统的合成方法在生物体中原位生成NIR-II荧光团。

研究组报道了一种创新的策略，在温和的条件下，以β-氯丙烯醛衍生物（Pre-Hcy）和间氨基噻吩为前体，制备了具有高转化效率（高达86%）的NIR-II半花青碱（NIR-II-Hcy）。有趣的是，该方法可推广到活体小鼠，酸性微环境有利于NIR-II-Hcy （k_{pH = 6.0}/k_{pH = 8.0} =10）的快速生成。

此外，通过利用二硫键的形成/裂解和酸性微环境，原位生成NIR-II- hcy使激活受到谷胱甘肽（GSH）和H⁺的控制，从而实现高对比度和判别性的体内肿瘤成像，本工作建立了肿瘤微环境驱动的NIR-II荧光发生的第一个范例。这一新发现将促进NIR-II染料更简单、更快的合成，在生物医学研究和临床诊断中具有广泛的应用。

附：英文原文

Title: Controllable in-situ Synthesis of NIR-II Hemicyanine in Living Organisms for Efficient Tumor Imaging

Author: Yujie Huang, Liping Wang, Qiumei Huang, Bangping Hu, Qinian Liu, Jing Wang, Xing-Can Shen, Hua Chen

Issue&Volume: 2025-06-24

Abstract: Second near-infrared region (NIR-II) small-molecule fluorophores hold great promise for biomedical imaging because of their well-defined chemical structures, superior metabolic properties, deep tissue penetration, and unprecedented clarity. However, it is impossible to apply conventional synthesis methods for the in-situ generation of NIR-II fluorophores in living organisms because of the need for high temperatures, strong acids or bases, and anhydrous conditions. Herein, we report an innovative strategy to create NIR-II hemicyanine (NIR-II-Hcy) with high conversion efficiency (up to 86%) under mild conditions, using β-chloroacroleins derivatives (Pre-Hcy) and meta-aminothiophenol as precursors without harsh conditions. Interestingly, this method can be extended to live mice, and the acidic microenvironment is conducive to the rapid production of NIR-II-Hcy (kpH = 6.0/kpH = 8.0 =10). Furthermore, by leveraging the formation/cleavage of disulfide bonds and the acidic microenvironment, the in-situ generation of NIR-II-Hcy enables the activation to be controlled by glutathione (GSH) and H+, thereby enabling high-contrast and discriminative in vivo tumor imaging, and this work establishes the first paradigm for tumor microenvironment-driven NIR-II fluorogenesis. This is a novel finding that will facilitate simpler and faster synthesis of NIR-II dyes with broad applications in biomedical research and clinical diagnostics.

DOI: 10.1002/cjoc.70160

Source: https://onlinelibrary.wiley.com/doi/10.1002/cjoc.70160