Nucleic Acid-Functionalized Metal-Organic Framework-Based Homogeneous Electrochemical Biosensor for Simultaneous Detection of Multiple Tumor Biomarkers
Nucleic Acid-Functionalized Metal-Organic Framework-Based Homogeneous Electrochemical Biosensor for Simultaneous Detection of Multiple Tumor Biomarkers
复制标题
基于核酸功能化金属有机框架的均相电化学生物传感器，用于同时检测多种肿瘤生物标志物
DOI：
10.1021/acs.analchem.8b05599
复制
发表时间：
2019-03-05
影响因子：
7.4
通讯作者：
Li, Feng
中科院分区：
文献类型：
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作者：
Chang, Jiafu;Wang, Xin;Li, Feng
同时检测多种肿瘤生物标志物对早期、准确的肿瘤诊断有很大的需求。均相电化学生物传感器已被证明具有高灵敏度，但实现多种肿瘤生物标志物的同时检测仍然是一个挑战。在此，我们开发了一种基于功能化金属有机框架（MOFs）的新型同质电化学生物传感器，用于同时检测多种肿瘤生物标志物。以多孔UI0-66-NH2作为负载电活性染料的纳米容器，dsDNA作为封盖的看门人，制备了功能化MOFs。在这种情况下，制备了两个功能化mof (MB@UTO和TMB@UI0)，并将其用于同时检测let 7a和miRNA-21，作为概念验证分析物。P-X与目标mirna的识别和杂交促进RNA - DNA复合物的产生，这些复合物从mof中分离出来，使电活性染料得以释放。与目标miRNA缺失的情况相比，记录到两个更强的信号，并且依赖于目标miRNA浓度。因此，我们实现了let-7a和minRNA-21的同时检测，检测限分别降至3.6和8.2 fM，与目前报道的专注于单个miRNA检测的策略相当或更低。此外，所提出的生物传感器也已成功地应用于同时检测血清样品中添加的目标mirna。因此，该策略有望为早期准确诊断癌症提供更多信息，在疾病诊断和临床生物医学中具有重要应用价值。
Simultaneous detection of multiple tumor biomarkers is in great demand for early and accurate cancer diagnosis. A homogeneous electrochemical biosensor has been proven to possess high sensitivity, but achieving simultaneous detection of multiple tumor biomarkers is still a challenge. Herein, we develop a novel homogeneous electrochemical biosensor for simultaneous detection of multiple tumor biomarkers based on the functionalized metal organic frameworks (MOFs). The functionalized MOFs were prepared by using porous UI0-66-NH2 as nanocontainer to load electroactive dyes and dsDNA as a gatekeeper to cap MOFs. In this context, two functionalized MOFs (MB@UTO and TMB@UI0) were fabricated and applied to simultaneous detection of let 7a and miRNA-21, used as the proof-of-concept analytes. The recognition and hybridization of P-X with target miRNAs impel the generation of RNA DNA complexes, which separated from MOFs and allowed the electroactive dyes to be released. In comparison with the case when target miRNAs are absent, two stronger signals are recorded, and dependent on target miRNA concentrations. Thus, simultaneous detection of let-7a and minRNA-21 is achieved, with detection limits down to 3.6 and 8.2 fM, respectively, comparable or lower than those of reported strategies that concentrated on single miRNA detection. Moreover, the proposed biosensor has also been successfully applied for simultaneous detection of target miRNAs spiked in serum samples. Therefore, the proposed strategy was expected to provide more information for early and accurate cancer diagnosis and was an useful application in disease diagnosis and clinical biomedicine.