背景:谷胱甘肽(GSH),细胞内的一种高度丰富的硫醇化合物,在生理过程中起着关键作用,并与癌症密切相关。在分子成像技术中,大多数探头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的存在可以中和ROS,降低PDT的治疗效果,因此通常导致不令人满意的治疗效果。因此,因此,研制一种检测GSH和诊断治疗肿瘤的双模态探针势在必行。
结果:在这项研究中,我们合成了一种新颖的双模态探针,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,和生物素作为肿瘤靶向部分。与GSH反应后,探针在820nm处发射NIR荧光并产生PA信号。重要的是,该反应激活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)的疗效显着增强。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,联合的肿瘤靶向能力和PDT/PTT协同治疗可提高肿瘤的治疗效果并促进其消融。
结论:合成了一种新型的肿瘤靶向和双模态成像探针(Cy-Bio-GSH),对GSH表现出显著的灵敏度和选择性,使细胞中GSH的可视化以及正常细胞和癌细胞之间的分化。Cy-Bio-GSH增强PDT/PTT,有效杀死癌细胞,并消融小鼠的肿瘤。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协同治疗为癌症诊断和治疗提供了关键工具。
BACKGROUND: 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.
RESULTS: 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.
CONCLUSIONS: 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.