Assembly of Black Phosphorus Nanosheets and MOF to Form Functional Hybrid Thin-Film for Precise Protein Capture, Dual-Signal and Intrinsic Self-Calibration Sensing of Specific Cancer-Derived Exosomes
Assembly of Black Phosphorus Nanosheets and MOF to Form Functional Hybrid Thin-Film for Precise Protein Capture, Dual-Signal and Intrinsic Self-Calibration Sensing of Specific Cancer-Derived Exosomes
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DOI：
10.1021/acs.analchem.9b05583
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发表时间：
2020-02-04
影响因子：
7.4
通讯作者：
Gui, Rijun
中科院分区：
文献类型：
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作者：
Sun, Yujiao;Jin, Hui;Gui, Rijun
外泌体作为一种新兴的非侵入性生物标志物，在癌症筛查、癌症相关免疫反应和生理过程中发挥着重要作用。癌细胞来源的外泌体的灵敏、特异和高效检测对于患者的早期癌症诊断具有重要意义。本工作基于功能混合薄膜平台开发了一种新型的双信号和内在自校准的外泌体适体传感器。该平台通过在氧化铟锡（ITO）切片上简单组装黑磷纳米片（BPNS）和二茂铁（Fc）掺杂的金属有机框架（ZIF-67），然后在ITO切片上组合亚甲蓝（MB）标记的单链DNA适体来构建。所得适体-BPNS/Fc/ZIF-67/ITO平台具有MB（标记在适体上）和Fc（掺杂到ZIF-67中）的双重氧化还原信号响应。在特定的癌细胞来源的外泌体的存在下，MB的氧化还原电流规律性地降低，而Fc（作为参考）的氧化还原电流几乎没有变化。实现了内在自校准适体传感器，并能够灵敏地检测外泌体，检测限低至100个粒子mL（-1）。具有精确蛋白捕获能力的适体传感器可以有效地确定来自健康个体和乳腺癌患者的实际人血清和血浆样品中的特定癌细胞来源的外泌体。鉴于其优异的性能，这种适体传感器可以扩展到来自细胞系外泌体的多种生物标志物，并且有利于探索用于高性能检测来自不同类型癌细胞的外泌体的先进技术。这项工作促进了当前早期癌症筛查和临床诊断技术的发展。
As the emerging and noninvasive biomarkers, exosomes play an important role in cancer screening, cancer-related immune response, and the physiological process. The sensitive, specific, and efficient detection of cancer cell-derived exosomes is of significance for early cancer diagnosis of patients. This work developed a novel dual-signal and intrinsic self-calibration aptasensor of exosomes based on a functional hybrid thin-film platform. This platform was constructed via facile assembly of black phosphorus nanosheets (BPNSs) and ferrocene (Fc)-doped metal-organic frameworks (ZIF-67) on indium tin oxide (ITO) slice, followed by combining methylene blue (MB)-labeled single- strand DNA aptamer on ITO slice. The resultant aptamer-BPNSs/Fc/ZIF-67/ITO platform had dual redox-signal responses of MB (labeled on aptamer) and Fc (doped into ZIF-67). In the presence of specific cancer cell-derived exosomes, the redox current of MB regularly reduced and that of Fc (as reference) hardly changed. An intrinsic self-calibration aptasensor was achieved and enabled sensitive detection of exosomes, showing a limit of detection down to 100 particles mL(-1). The aptasensor with a capability of precise protein capture can efficiently determine specific cancer cell-derived exosomes in practical human serum and plasma samples from healthy individuals and breast cancer patients. In light of excellent performances, this aptasensor can be expanded to multiple biomarkers from cell line exosomes and is beneficial for exploring advanced techniques for high-performance detection of exosomes derived from different types of cancer cells. This work promotes the development of current techniques for early cancer screening and clinical diagnosis.