用于检测潜在 COVID-19 生物标志物和药物的 MOF/DNA 发光传感平台,Chemical Science

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用于检测潜在 COVID-19 生物标志物和药物的 MOF/DNA 发光传感平台
Chemical Science ( IF 7.6 ) Pub Date : 2023-04-19 , DOI: 10.1039/d3sc00106g
Xinrui Wang ₁ , Gilles Clavier ₂ , Yan Zhang ₃ , Kamal Batra ₄ , Nanan Xiao ₃ , Guillaume Maurin ₄ , Bin Ding ₅ , Antoine Tissot ₁ , Christian Serre ₁

Affiliation

COVID-19 已经影响了全世界人们的生活。白介素 6 (IL-6) 是人体体液中重要的 COVID-19 生物标志物，可作为实时监测 COVID-19 的参考，从而降低病毒传播的风险。另一方面，奥司他韦是一种潜在的 COVID-19 治疗药物，但其过度使用容易导致危险的副作用，需要对其进行实时体液监测。为此，合成了一种新的钇金属有机框架 (Y-MOF)，其中 5-(4-(咪唑-1-基)苯基) 间苯二甲酸连接基包含一个能够与 DNA 强烈相互作用的大芳香骨架通过 π-π 堆叠相互作用进行排序，这使得构建基于 DNA 功能化 MOF 的独特传感器具有吸引力。MOF/DNA 序列混合发光传感平台具有与高 Förster 共振能量转移 (FRET) 效率相关的优异光学特性。此外，为了构建双发射传感平台，已将具有可与 IL-6 特异性相互作用的茎环结构的 5'-羧基荧光素 (FAM) 标记的 DNA 序列 (S2) 与 Y-MOF 相关联。由此产生的 Y-MOF@S2 表现出对人体体液中 IL-6 的有效比率检测，具有极高的K _sv值 4.3 × 10 ⁸ M ⁻¹和 70 pM 的低检测限 (LOD)。最后，Y-MOF@S2@IL-6 混合平台允许高灵敏度检测奥司他韦（K _sv值高达 5.6 × 10 ⁵ M ^-1，LOD 为 54 nM），因为奥司他韦可以断开由 S2 构建的环状茎结构，从而对 Y-MOF@S2@IL-6 产生强烈的猝灭作用。奥司他韦和 Y-MOF 之间相互作用的性质已通过密度泛函理论计算得到阐明，而 IL-6 和奥司他韦双重检测的传感机制已根据发光寿命测试和共聚焦激光扫描显微镜破译。

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A MOF/DNA luminescent sensing platform for detection of potential COVID-19 biomarkers and drugs

COVID-19 has afflicted people's lives worldwide. Interleukin-6 (IL-6) is an important COVID-19 biomarker in human body fluids that can be used as a reference to monitor COVID-19 in real-time and therefore to reduce the risk of virus transmission. On the other hand, oseltamivir is a potential COVID-19 curing drug, but its overuse easily leads to hazardous side effects, calling for its real time monitoring in body fluids. For these purposes, a new yttrium metal–organic framework (Y-MOF) has been synthesized, in which the 5-(4-(imidazole-1-yl)phenyl)isophthalic linker contains a large aromatic backbone capable of strongly interacting with DNA sequences through π–π stacking interactions, which makes it appealing to build a unique sensor based on DNA functionalized MOFs. The MOF/DNA sequence hybrid luminescent sensing platform presents excellent optical properties associated with a high Förster resonance energy transfer (FRET) efficiency. Furthermore, to construct a dual emission sensing platform, a 5′-carboxylfluorescein (FAM) labeled DNA sequence (S2) with a stem-loop structure that can specifically interact with IL-6 has been associated with the Y-MOF. The resulting Y-MOF@S2 exhibits an efficient ratiometric detection of IL-6 in human body fluids with an extremely high K_sv value 4.3 × 10⁸ M⁻¹ and a low detection limit (LOD) of 70 pM. Finally, the Y-MOF@S2@IL-6 hybrid platform allows the detection of oseltamivir with high sensitivity (K_sv value is as high as 5.6 × 10⁵ M⁻¹ and LOD is 54 nM), due to the fact that oseltamivir can disconnect the loop stem structure constructed by S2, leading to a strong quenching effect towards Y-MOF@S2@IL-6. The nature of the interactions between oseltamivir and Y-MOF has been elucidated using density functional theory calculations while the sensing mechanism for the dual detection of IL-6 and oseltamivir has been deciphered based on luminescence lifetime tests and confocal laser scanning microscopy.

更新日期：2023-04-19

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