Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, PR China.
Wuxi School of Medicine, Jiangnan University, Wuxi 214122, PR China.
Nanoscale. 2021 Sep 17;13(35):15067-15073. doi: 10.1039/d1nr02821a.
The most efficient approach for cancer identification and monitoring is the detection of cancer-associated protein biomarkers but an accurate diagnosis requires multiple analyses. Glycosylation profiling can provide important biological information since different glycoforms are involved in malignant transformation. Here, a near-infrared (NIR) light activated fluorescence resonance energy transfer (FRET) strategy for the efficient and reliable simultaneous dual imaging of the mucin 1 (MUC1) protein backbone and MUC1-specific sialic acid (Sia) is reported. MUC1, an important tumor biomarker, is overexpressed and under-glycosylated in most tumor cells. Two aptamer-functionalized nanoprobes, Cy5-labeled Sia aptamer-functionalized gold nanostars (Sia-GNSs) and MUC1 aptamer-functionalized quantum dots (MUC1-QDs), were successfully constructed with high specificity and biocompatibility. Upon excitation with NIR light, Sia-GNSs endothermically released the Cy5-labeled Sia aptamer that specifically binds to Sia. The Cy5 fluorescence can be observed due to the FRET effect when the Cy5-labeled Sia aptamer and MUC1-QDs bind to the same MUC1 molecule. Dual imaging and relative quantification of MUC1 and its sialylation were achieved , and in clinical tissue samples. This efficient platform allows for the simultaneous detection of protein biomarkers and their glycosylation pattern, with significant potential for clinical cancer diagnostics.
用于癌症识别和监测的最有效方法是检测与癌症相关的蛋白质生物标志物，但准确的诊断需要进行多次分析。糖基化分析可以提供重要的生物学信息，因为不同的糖型参与了恶性转化。在这里，报道了一种近红外（NIR）光激活的荧光共振能量转移（FRET）策略，用于高效可靠地同时对粘蛋白 1（MUC1）蛋白主链和 MUC1 特异性唾液酸（Sia）进行双重成像。MUC1 是一种重要的肿瘤标志物，在大多数肿瘤细胞中过度表达和低聚糖化。两种适配体功能化的纳米探针，Cy5 标记的 Sia 适配体功能化的金纳米星（Sia-GNSs）和 MUC1 适配体功能化的量子点（MUC1-QDs），具有高特异性和生物相容性，被成功构建。当用近红外光激发时，Sia-GNSs 会吸收热量并释放出特异性结合 Sia 的 Cy5 标记的 Sia 适配体。当 Cy5 标记的 Sia 适配体与 MUC1-QDs 结合到同一 MUC1 分子上时，由于 FRET 效应，可以观察到 Cy5 荧光。在临床组织样本中实现了 MUC1 及其唾液酸化的双重成像和相对定量。这种高效的平台允许同时检测蛋白质生物标志物及其糖基化模式，具有显著的临床癌症诊断潜力。
