Glutathione (GSH), a highly abundant thiol compound within cells, plays a critical role in physiological processes and exhibits close correlation with cancer. Among molecular imaging technologies, most probes have relatively short emission wavelengths and lack photoacoustic imaging (PA) capability, resulting in the inability to obtain tissue images with high penetration depth. The presence of GSH in the tumor microenvironment neutralizes ROS, diminishing the therapeutic effect of PDT, thus resulting in often unsatisfactory therapeutic efficacy. Therefore, it is imperative to develop a dual-modal probe for the detection of GSH and the diagnosis and treatment of cancer. In this study, we synthesized a novel dual-modal probe, Cy-Bio-GSH, utilizing near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging techniques for GSH detection. The probe integrates cyanine dye as the fluorophore, nitroazobenzene as the recognition moiety, and biotin as the tumor-targeting moiety. Upon reacting with GSH, the probe emits NIR fluorescence at 820 nm and generates a PA signal. Significantly, this reaction activates the photodynamic and photothermal properties of the probe. By depleting GSH and employing a synergistic photothermal therapy (PTT) treatment, the therapeutic efficacy of photodynamic therapy (PDT) is remarkably enhanced. In-vivo experiments confirm the capability of the probe to detect GSH via NIRF and PA imaging. Notably, the combined tumor-targeting ability and PDT/PTT synergistic therapy enhance therapeutic outcomes for tumors and facilitate their ablation. A novel tumor-targeting and dual-modal imaging probe (Cy-Bio-GSH) is synthesized, exhibiting remarkable sensitivity and selectivity to GSH, enabling the visualization of GSH in cells and the differentiation between normal and cancer cells. Cy-Bio-GSH enhances PDT/PTT with effective killing of cancer cells and makes the ablation of tumors in mice. This work represents the first tumor-targeting probe for GSH detection, and provides crucial tool for cancer diagnosis and treatment by dual-modal imaging with improved PDT/PTT synergistic therapy.

中文翻译：

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谷胱甘肽激活生物素靶向双模式成像探针，具有改进的 PDT/PTT 协同治疗


谷胱甘肽（GSH）是细胞内含量丰富的硫醇化合物，在生理过程中发挥着关键作用，并与癌症密切相关。在分子成像技术中，大多数探针的发射波长相对较短，缺乏光声成像（PA）能力，导致无法获得高穿透深度的组织图像。肿瘤微环境中GSH的存在会中和ROS，降低PDT的治疗效果，从而导致治疗效果往往不理想。因此，开发用于GSH检测和癌症诊断和治疗的双模态探针势在必行。在这项研究中，我们合成了一种新型双模态探针 Cy-Bio-GSH，利用近红外荧光 (NIRF) 和光声 (PA) 成像技术进行 GSH 检测。该探针整合了花青染料作为荧光团、硝基偶氮苯作为识别部分、生物素作为肿瘤靶向部分。与 GSH 反应后，探针会发出 820 nm 的 NIR 荧光并产生 PA 信号。值得注意的是，该反应激活了探针的光动力和光热特性。通过消耗GSH并采用协同光热疗法（PTT）治疗，光动力疗法（PDT）的治疗效果显着增强。体内实验证实了探针通过 NIRF 和 PA 成像检测 GSH 的能力。值得注意的是，肿瘤靶向能力和PDT/PTT协同治疗的结合可以增强肿瘤的治疗效果并促进肿瘤的消融。 合成了一种新型肿瘤靶向双模态成像探针（Cy-Bio-GSH），对 GSH 表现出卓越的敏感性和选择性，能够实现细胞中 GSH 的可视化以及正常细胞和癌细胞的区分。 Cy-Bio-GSH增强PDT/PTT，有效杀伤癌细胞，使小鼠肿瘤消融。这项工作代表了第一个用于 GSH 检测的肿瘤靶向探针，并通过双模态成像和改进的 PDT/PTT 协同疗法为癌症诊断和治疗提供了重要工具。