肿瘤微环境特异性成像对癌症的精准诊断至关重要，传统单模态成像技术难以兼顾高灵敏度与高空间分辨率. 本研究设计并合成了一种cRGD肽靶向、硝基还原酶（NTR）响应的半花菁-¹⁹F双模态探针Cy-F-cRGD. 通过系统筛选不同含氟基团，发现邻位双氟结构可产生显著的¹⁹F化学位移变化（Δδ_F = 10.87）. NTR响应后半花菁单元的紫外吸收红移80 nm，荧光强度增强约90倍，实现了光学信号的“关-开”切换. 本研究为发展智能响应型多模态探针提供了新的设计策略. 

Specific imaging of the tumor microenvironment is critical for precise cancer diagnosis, yet conventional single-modal imaging techniques struggle to combine high sensitivity with high spatial resolution. This study designed and synthesized a cRGD peptide-targeted, nitroreductase (NTR)-responsive hemicyanine-¹⁹F dual-modal probe, Cy-F-cRGD. Through systematic screening of different fluorine-containing groups, we found that an ortho-difluoro structure induced a remarkable ¹⁹F chemical shift change (Δδ_F = 10.87). Concurrently, the hemicyanine unit exhibited an 80 nm red-shift in absorption and a 90-fold fluorescence enhancement, achieving an optical “off-on” signal switch. This work offers a new design strategy for developing intelligently responsive multimodal probes.