Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha 410081, P. R. China.
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People's Hospital), Hunan Normal University, Changsha 410005, P. R. China.
Anal Chem. 2024 May 7;96(18):7248-7256. doi: 10.1021/acs.analchem.4c00922. Epub 2024 Apr 24.
Ferroptosis modulation is a powerful therapeutic option for pancreatic ductal adenocarcinoma (PDAC) with a low 5-year survival rate and lack of effective treatment methods. However, due to the dual role of ferroptosis in promoting and inhibiting pancreatic tumorigenesis, regulating the degree of ferroptosis is very important to obtain the best therapeutic effect of PDAC. Biothiols are suitable as biomarkers of imaging ferroptosis due to the dramatic decreases of biothiol levels in ferroptosis caused by the inhibited synthesis pathway of glutathione (GSH) and the depletion of biothiol by reactive oxygen species. Moreover, a very recent study reported that cysteine (Cys) depletion can lead to pancreatic tumor ferroptosis in mice and may be employed as an effective therapeutic strategy for PDAC. Therefore, visualization of biothiols in ferroptosis of PDAC will be helpful for regulating the degree of ferroptosis, understanding the mechanism of Cys depletion-induced pancreatic tumor ferroptosis, and further promoting the study and treatment of PDAC. Herein, two biothiol-activable near-infrared (NIR) fluorescent/photoacoustic bimodal imaging probes (HYD-BX and HYD-DX) for imaging of pancreatic tumor ferroptosis were reported. These two probes show excellent bimodal response performances for biothiols in solution, cells, and tumors. Subsequently, they have been employed successfully for real-time visualization of changes in concentration levels of biothiols during the ferroptosis process in PDAC cells and HepG2 cells. Most importantly, they have been further applied for bimodal imaging of ferroptosis in pancreatic cancer in mice, with satisfactory results. The development of these two probes provides new tools for monitoring changes in concentration levels of biothiols in ferroptosis and will have a positive impact on understanding the mechanism of Cys depletion-induced pancreatic tumor ferroptosis and further promoting the study and treatment of PDAC.
铁死亡调节是一种有前途的治疗策略，可用于胰腺导管腺癌 (PDAC)，这种癌症的 5 年生存率低，且缺乏有效的治疗方法。然而，由于铁死亡在促进和抑制胰腺肿瘤发生中的双重作用，调节铁死亡的程度对于获得 PDAC 的最佳治疗效果非常重要。生物硫醇由于谷胱甘肽 (GSH) 合成途径受阻和活性氧耗竭导致生物硫醇水平急剧下降，因此非常适合作为铁死亡成像的生物标志物。此外，最近的一项研究报道，半胱氨酸 (Cys) 的耗竭可导致小鼠胰腺肿瘤发生铁死亡，可能成为 PDAC 的一种有效治疗策略。因此，PDAC 铁死亡中生物硫醇的可视化将有助于调节铁死亡的程度，深入了解 Cys 耗竭诱导的胰腺肿瘤铁死亡的机制，并进一步促进 PDAC 的研究和治疗。在此，报道了两种用于胰腺肿瘤铁死亡成像的生物硫醇激活型近红外 (NIR) 荧光/光声双模成像探针 (HYD-BX 和 HYD-DX)。这两种探针在溶液、细胞和肿瘤中对生物硫醇均表现出优异的双模响应性能。随后，它们成功地用于实时可视化 PDAC 细胞和 HepG2 细胞中铁死亡过程中生物硫醇浓度水平的变化。最重要的是，它们进一步应用于小鼠胰腺癌的双模态成像，取得了令人满意的结果。这两种探针的开发为监测铁死亡过程中生物硫醇浓度水平的变化提供了新的工具，将有助于深入了解 Cys 耗竭诱导的胰腺肿瘤铁死亡的机制，并进一步促进 PDAC 的研究和治疗。
