Because of insufficient information, a single biomarker is not sufficient for early diagnosis of cancer, whereas sensitive and selective detection of multiple biomolecules can significantly reduce analysis time, sample size, and accurately perform cell screening in early cancer. Therefore, the development of a noninvasive strategy that can simultaneously quantify multiple biomarkers (i.e., nucleic acids, proteins, and small molecules) in a single cell is particularly important. Herein, a universal sensing system (functional DNA@mesoporous silica nanoparticles (MSN)–Black Hole Quencher–rhodamine 6G (RhB), FDSBR), which is based on the combination of functionalized DNA and smart responsive nanomaterial, was successfully constructed. After incubation with the cells, different types of targets trigger the strand displacement reaction to release the fluorophore-labeled nucleic acids as the output signals to reflect the intracellular level of the telomerase and adenosine triphosphate (ATP), respectively. Simultaneously, intracellular miR-21 can be clearly indicated by the restored fluorescence of RhB when the caged double-stranded DNA was substituted into single-stranded DNA to open the pore. The concentrations of intracellular telomerase, miR-21, and ATP were identified successfully in three cell lines at the single-cell level. The results show that the contents of three biomolecules have significant differences in the three model cell lines and provide a promising route for developing innovative early disease diagnosis and cell screening assay.

中文翻译：

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活细胞中多种生物分子的定量检测和成像，用于细胞筛选。

由于信息不足，单个生物标记物不足以早期诊断癌症，而对多种生物分子进行灵敏且选择性的检测可以显着减少分析时间，样本量并准确地进行早期癌症的细胞筛选。因此，开发了一种可以同时量化多个生物标记物（即（单个核酸，核酸，蛋白质和小分子）特别重要。在此，基于功能化DNA和智能响应纳米材料的组合，成功构建了通用传感系统（功能性DNA @介孔二氧化硅纳米粒子（MSN）-黑洞猝灭剂-若丹明6G（RhB），FDSBR）。与细胞孵育后，不同类型的靶标会触发链置换反应，释放出荧光团标记的核酸，作为输出信号，分别反映端粒酶和三磷酸腺苷（ATP）的细胞内水平。同时，当将笼中的双链DNA替换为单链DNA打开孔时，RhB的恢复荧光可以清楚地表明细胞内miR-21。在单细胞水平成功鉴定了三种细胞系中细胞内端粒酶，miR-21和ATP的浓度。结果表明，三种生物分子的含量在三种模型细胞系中具有显着差异，为开发创新的早期疾病诊断和细胞筛选测定方法提供了有希望的途径。