早期治疗显著提高肝癌患者的生存率,因此,开发肝癌的早期诊断方法迫在眉睫。肝癌可以从病毒性肝炎发展而来,酒精性肝,脂肪肝,从而使上述疾病具有共同的特征,如粘度升高,活性氧,和活性氮物种。因此,其他肝脏疾病和肝癌之间的准确区分是一个最重要的实际需要和具有挑战性。已经报道了许多荧光探针通过检测单个生物标志物来诊断肝癌。但是这些探针在复杂的生物系统中缺乏对肝癌的特异性。显然,使用多种肝癌生物标志物作为判断的基础,可以显著提高诊断的准确性.在这里,我们报道了第一个荧光探针,LD-TCE,以高灵敏度和选择性依次检测肝癌细胞中的羧酸酯酶(CE)和脂滴极性,在0-6U/mL范围内线性检测CE,并响应极性增强65倍的荧光。探针首先与CE反应并释放弱荧光,然后由于肝癌细胞中脂滴极性的降低而急剧增强。这种方法允许探针能够以更高的对比度和准确性对肝癌进行特异性成像。该探针成功实现了肝癌细胞的筛选和小鼠肝癌的精确鉴定。更重要的是,它不受肝纤维化的干扰,这是许多肝脏疾病的共同病理特征。我们认为LD-TCE有望成为肝癌早期诊断的有力工具。
Early treatment significantly improves the survival rate of liver cancer patients, so the development of early diagnostic methods for liver cancer is urgent. Liver cancer can develop from viral hepatitis, alcoholic liver, and fatty liver, thus making the above diseases share common features such as elevated viscosity, reactive oxygen species, and reactive nitrogen species. Therefore, accurate differentiation between other liver diseases and liver cancer is both a paramount practical need and challenging. Numerous fluorescent probes have been reported for the diagnosis of liver cancer by detecting a single biomarker, but these probes lack specificity for liver cancer in complex biological systems. Obviously, using multiple liver cancer biomarkers as the basis for judgment can dramatically improve diagnostic accuracy. Herein, we report the first fluorescent probe, LD-TCE, that sequentially detects
carboxylesterase (CE) and lipid droplet polarity in liver cancer cells with high sensitivity and selectivity, with linear detection of CE in the range of 0-6 U/mL and a 65-fold fluorescence enhancement in response to polarity. The probe first reacts with CE and releases weak fluorescence, which is then dramatically enhanced due to the decrease in lipid droplet polarity in liver cancer cells. This approach allows the probe to enable specific imaging of liver cancer with higher contrast and accuracy. The probe successfully achieved the screening of liver cancer cells and the precise identification of liver cancer in mice. More importantly, it is not disturbed by liver fibrosis, which is a common pathological feature of many liver diseases. We believe that the LD-TCE is expected to be a powerful tool for early diagnosis of liver cancer.