College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, China.
Department of Geratology, the Third Xiangya Hospital, Central South University, Changsha 410013, Hunan, China.
Talanta. 2019 Jul 1;199:238-243. doi: 10.1016/j.talanta.2019.02.014. Epub 2019 Feb 5.
Human epidermal growth factor receptor-2 (HER2) has been recognized as an important biomarker for the early diagnosis and management of breast cancer. However, there is still challenge in the clinical detection of HER2. In this work, a simple strategy for "turn on" fluorescent detection of HER2 with ultra-sensitivity and high specificity was developed. Herein, HER2-binding aptamer (HApt) and DNA2 containing G-rich sequences, templated sequences for Ag nanoclusters (AgNCs), and complementary bases at both ends were involved to achieve the double stranded DNA templated AgNCs (dsDNA-AgNCs) as a fluorescence probe for HER2 detection. In the presence of HER2, the highly specific binding of HER2 to HApt caused HApt separating from dsDNA-AgNCs, resulting in the folding of DNA2-AgNCs because of the complementary bases at both ends, which led to AgNCs' proximity to G-rich sequences, and therefore the enhanced fluorescence intensity. By monitoring the change in fluorescence signal (ΔF), HER2 was measured, and a linear range from 8.5 fM to 225 fM with a limit of detection (LOD) 0.0904 fM was obtained. More significantly, the detection of HER2 in serum samples was achieved with high accuracy, and the breast cancer patients were successfully discriminated from healthy persons. In summary, this strategy is simple, time-saving, cost-effective, ultrasensitive, specific, universal and more applicable for the detection of HER2. Therefore, we expect this present aptasensor can be used in the clinical detection of biomakers, which lays a potential foundation for the early diagnosis of cancer.
人表皮生长因子受体 2(HER2)已被认为是乳腺癌早期诊断和治疗的重要生物标志物。然而,HER2 的临床检测仍然具有挑战性。在这项工作中,开发了一种简单的超灵敏和高特异性“开启”荧光检测 HER2 的策略。在此,涉及 HER2 结合适体(HApt)和含有 G-丰富序列的 DNA2、Ag 纳米团簇(AgNCs)的模板序列以及两端的互补碱基,以实现双链 DNA 模板 AgNCs(dsDNA-AgNCs)作为用于 HER2 检测的荧光探针。在存在 HER2 的情况下,HER2 与 HApt 的高度特异性结合导致 HApt 从 dsDNA-AgNCs 中分离出来,由于两端的互补碱基,导致 DNA2-AgNCs 折叠,从而导致 AgNCs 接近 G-丰富序列,从而增强了荧光强度。通过监测荧光信号的变化(ΔF)来测量 HER2,并获得了从 8.5 fM 到 225 fM 的线性范围,检测限(LOD)为 0.0904 fM。更重要的是,通过高准确度实现了血清样本中 HER2 的检测,并成功区分了乳腺癌患者和健康人。总之,该策略简单、省时、经济高效、超灵敏、特异性高、通用,更适用于 HER2 的检测。因此,我们期望本适体传感器可用于生物标志物的临床检测,为癌症的早期诊断奠定了潜在基础。