湖南大学张晓兵团队用于准确体内肿瘤转移成像NIR-II G-四重荧光探针的合理设计。相关研究成果于2024年4月22日发表在国际顶尖学术期刊《美国化学会杂志》。

G-quadruplex（G4）的精确体内成像对于了解G4-相关疾病（如癌症）的出现和进展至关重要。然而，现有的体内G4荧光探针主要在近红外区（NIR-I）内工作，由于发射波长短，这限制了它们的应用精度。向第二近红外（NIR-II）荧光成像的转变引起了人们的极大兴趣，因为它提供了减少的自发荧光和更深的组织穿透，从而促进了更准确的体内成像。尽管如此，由于缺乏有效的探针设计策略，NIR-II G4探针的发展受到了阻碍。

该文中，研究人员通过“逐步”的合理设计方法，成功开发出了NIRG-2，这是第一个具有NIR-II发射的小分子荧光探针，专门用于体内G4检测。分子对接计算表明，NIRG-2与G4结构形成稳定的氢键和强的π–π相互作用，有效抑制扭曲的分子内电荷转移（TICT），从而选择性地照亮G4结构。由于其NIR-II发射（940nm）、大的斯托克斯位移（90nm）和高选择性，NIRG-2为体内G4检测提供了高达47倍的荧光增强和5mm的组织成像深度，显著优于现有的G4探针。利用NIRG-2，研究人员首次实现了通过淋巴结和精确肿瘤切除的肿瘤转移的高对比度可视化。此外，NIRG-2在评估癌症淋巴转移模型的手术和药物治疗效果方面被证明是非常有效和可靠的。

该项研究不仅为深入了解G4相关疾病提供了一个重要的分子工具，而且为开发临床NIR-II G4活化探针提供了一种有前景的策略。

附：英文原文

Title: Rational Design of NIR-II G-Quadruplex Fluorescent Probes for Accurate In Vivo Tumor Metastasis Imaging

Author: Ren-Xuan Wang, Yifeng Ou, Yushi Chen, Tian-Bing Ren, Lin Yuan, Xiao-Bing Zhang

Issue&Volume: April 22, 2024

Abstract: Accurate in vivo imaging of G-quadruplexes (G4) is critical for understanding the emergence and progression of G4-associated diseases like cancer. However, existing in vivo G4 fluorescent probes primarily operate within the near-infrared region (NIR-I), which limits their application accuracy due to the short emission wavelength. The transition to second near-infrared (NIR-II) fluorescent imaging has been of significant interest, as it offers reduced autofluorescence and deeper tissue penetration, thereby facilitating more accurate in vivo imaging. Nonetheless, the advancement of NIR-II G4 probes has been impeded by the absence of effective probe design strategies. Herein, through a “step-by-step” rational design approach, we have successfully developed NIRG-2, the first small-molecule fluorescent probe with NIR-II emission tailored for in vivo G4 detection. Molecular docking calculations reveal that NIRG-2 forms stable hydrogen bonds and strong π–π interactions with G4 structures, which effectively inhibit twisted intramolecular charge transfer (TICT) and, thereby, selectively illuminate G4 structures. Due to its NIR-II emission (940 nm), large Stokes shift (90 nm), and high selectivity, NIRG-2 offers up to 47-fold fluorescence enhancement and a tissue imaging depth of 5 mm for in vivo G4 detection, significantly outperforming existing G4 probes. Utilizing NIRG-2, we have, for the first time, achieved high-contrast visualization of tumor metastasis through lymph nodes and precise tumor resection. Furthermore, NIRG-2 proves to be highly effective and reliable in evaluating surgical and drug treatment efficacy in cancer lymphatic metastasis models. We are optimistic that this study not only provides a crucial molecular tool for an in-depth understanding of G4-related diseases in vivo but also marks a promising strategy for the development of clinical NIR-II G4-activated probes.

DOI: 10.1021/jacs.3c13851

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.3c13851