Zhang Shuping, Liu Xingyue, Jiang Bang-Ping, Ji Shi-Chen, Chen Hua, Shen Xing-Can
Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Guangxi Key Laboratory of Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, P. R. China.
Key Laboratory of Functional Organometallic Materials of College of Hunan Province, College of Chemistry and Materials Science, Hengyang Normal University, Hengyang 421008, P. R. China.
Anal Chem. 2025 Jul 1;97(25):13637-13645. doi: 10.1021/acs.analchem.5c02253. Epub 2025 May 30.
Tracking the quantitative evaluation of therapeutic efficiency in tumors is essential for the precision management of cancer patients. Theranostic probes, which integrate diagnostic molecular imaging and therapeutic capabilities into a single entity, can be used to monitor the treatment process and reflect the therapeutic effect. However, current theranostic probes lack precise quantitative evaluations due to the use of single-wavelength imaging during tumor therapy. Here we present a portal library of dual ratiometric single-molecule theranostic probes for precise tumor therapy through photothermal therapy (PTT) and quantitative evaluation of tumor cell death via ratiometric near-infrared fluorescence (NIRF) and ratiometric photoacoustic (PA) imaging. One optimal single-molecule dye is further modified into an activatable probe (AF-1F-NO), whose dual ratiometric NIRF/PA signal and photothermal activity are only activated in the presence of a tumor biomarker (nitroreductase). By eliciting a dual ratiometric response (NIRF/PA: NIRF/NIRF; PA/PA) to tumor hypoxia, the new probe acts as a hypoxia-activated PTT theranostic agent, enabling real-time quantitative evaluation during PTT. Thus, this study not only presents the first dual ratiometric single-molecule theranostic probe for PTT and real-time quantitative evaluation of therapeutic efficacy , but also opens up a promising paradigm for engineering other single-molecule dual ratiometric theranostic probes in combination with more therapeutic modalities for precision medicine.
追踪肿瘤治疗效果的定量评估对于癌症患者的精准管理至关重要。诊疗探针将诊断性分子成像和治疗能力整合于一体，可用于监测治疗过程并反映治疗效果。然而，由于在肿瘤治疗过程中使用单波长成像，目前的诊疗探针缺乏精确的定量评估。在此，我们展示了一个双比率单分子诊疗探针库，用于通过光热疗法（PTT）进行精确的肿瘤治疗，并通过比率近红外荧光（NIRF）和比率光声（PA）成像对肿瘤细胞死亡进行定量评估。一种最佳的单分子染料进一步被修饰成可激活探针（AF-1F-NO），其双比率NIRF/PA信号和光热活性仅在肿瘤生物标志物（硝基还原酶）存在时被激活。通过对肿瘤缺氧引发双比率响应（NIRF/PA：NIRF/NIRF；PA/PA），新探针作为一种缺氧激活的PTT诊疗剂，能够在PTT过程中进行实时定量评估。因此，本研究不仅展示了首个用于PTT和治疗效果实时定量评估的双比率单分子诊疗探针，还为结合更多治疗方式设计其他单分子双比率诊疗探针以实现精准医学开辟了一个有前景的范例。
