Breast cancer is the second cause of cancer mortality in women globally. Early detection, treatment, and metastasis monitoring are of great importance to favorable prognosis. Although conventional diagnostic methods, such as breast X-ray mammography and image positioning biopsy, are accurate, they could cause radioactive or invasive damage to patients. Liquid biopsy as a noninvasive method is convenient for repeated sampling in clinical cancer prognostic, metastatic evaluation, and relapse monitoring. MicroRNAs encased in exosomes circulating in biofluids are promising candidate cancer biomarkers because of their cancer-specific expression profiles. Here, we report an in situ detection of microRNA-1246 (miR-1246) in human plasma exosomes as breast cancer biomarker by a nucleic acid functionalized Au nanoflare probe. Needing neither time-consuming and costly isolation of exosomes from the plasma sample nor transfection means, the Au nanoflare probe can directly enter the plasma exosomes to generate fluorescent signal quantitatively by specifically targeting miR-1246. Only 40 μL of plasma is needed to incubate 4 h with the probe, giving signal sensitive enough to distinguish samples of breast cancer to normal control. Using plasma miR-1246 level detected by our assay as a marker, we differentiated 46 breast cancer patients from 28 healthy controls with 100% sensitivity and 92.9% specificity at the best cutoff. This simple, accurate, sensitive, and cost-effective liquid biopsy by the Au nanoflare probe is potent to be developed as a noninvasive breast cancer diagnostic assay for clinical adaption.

中文翻译：

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通过Au Nanoflare探针原位检测血浆外泌体MicroRNA-1246对乳腺癌的诊断

乳腺癌是全球女性癌症死亡的第二大原因。早期发现，治疗和转移监测对于良好的预后至关重要。尽管常规的诊断方法（如乳房X射线乳房X线照相术和图像定位活检）是准确的，但它们可能对患者造成放射性或浸润性损害。液体活检作为一种非侵入性方法，可方便地在临床癌症预后，转移评估和复发监测中进行重复采样。包裹在生物流体中循环的外泌体中的MicroRNA由于其特定于癌症的表达特征而成为有前途的候选癌症生物标志物。在这里，我们报告通过核酸功能化的Au纳米耀斑探针原位检测人类血浆外泌体中的microRNA-1246（miR-1246）作为乳腺癌的生物标志物。不需要耗时且昂贵的从血浆样品中分离外泌体，也不需要转染手段，Au纳米光斑探针可以直接进入血浆外泌体，通过特异性靶向miR-1246定量产生荧光信号。仅需40μL血浆即可与探针孵育4小时，信号灵敏度足以区分正常对照的乳腺癌样品。使用通过我们的检测方法检测到的血浆miR-1246水平作为标志物，我们以最佳截止率将100名敏感性和92.9％特异性的28名健康对照与46名乳腺癌患者区分开来。Au纳米光斑探针的这种简单，准确，灵敏且具有成本效益的液体活检技术很可能被开发为一种用于临床适应性的非侵入性乳腺癌诊断检测方法。