ECL金属-有机框架(MOF)生物传感平台用于肿瘤细胞分泌H2O2的测定

doi:10.6023/A21050223

摘要/Abstract

本工作借助金属-有机框架(MOF)结构, 通过配位作用实现对电化学发光(ECL)分子的空间有序组装, 获得了高性能ECL新材料, 发展了孔道限域效应和微纳空间ECL分子有序组装的协同增强ECL新策略. 具体而言, 以非共平面ECL分子1,1,2,2-四(4-羧基苯)乙烯(H₄TCPE)为配体采用一步水热法合成了具有优异ECL性能的新型MOF材料(Zr-TCPE). Zr-TCPE通过将发光配体H₄TCPE固定在MOF多孔材料上, 一方面其多孔结构可以促进限域空间内物质和电子的传递, 加快电化学反应的效率; 同时, MOF结构的配位键合作用限制了发光基团的自由转动与振动以及分子间的紧密堆积, 从而有效减少了非辐射弛豫和内滤效应. 和H₄TCPE的微纳晶体相比, Zr-TCPE的ECL强度提高了3.46倍, ECL效率提高了17.44倍. 采用Zr-TCPE构建了ECL生物传感平台, 成功实现了在药物刺激下肿瘤细胞释放过氧化氢(H₂O₂)的原位监测, 对临床检测肿瘤细胞具有指导意义.

关键词: 金属-有机框架材料, 1,1,2,2-四(4-羧基苯)乙烯, 电化学发光生物传感器, 肿瘤细胞, 过氧化氢

In this work, a kind of high-performance electrochemiluminescence (ECL) material was obtained with the assistant of metal-organic framework (MOF) structure, which realized the highly ordered assembly of ECL molecules in MOF structure, developing a new strategy of synergistically enhanced ECL. Specifically, it combined the advantages of both the pore confinement effect and the highly ordered assembly of ECL molecules in micro/nano space to enhance the ECL intensity and reaction efficiency. The proposed MOF material (abbreviated as Zr-TCPE) with excellent ECL performance was synthesized by a simple solvothermal synthesis technique employing the non-coplanar molecule 1,1,2,2-tetrachlorophenol- (4-carboxylic benzene)ethylene (H₄TCPE) as ligand and Zr₆ clusters through coordination interaction. Zr-TCPE with the porous structure can not only promote the mass transport and electron transfer in the confined micro/nano spaces, but also reduce the nonradiative relaxation and filtering effect as the H₄TCPE ligands were fixed on the rigid metal frame, restricting the free vibration/rotation and tight packing. Compared with the H₄TCPE micro/nano crystals prepared by reprecipitation method, the ECL intensity and efficiency of the Zr-TCPE increased by 3.46 times and 17.44 times with potential from 0 V to 1.4 V at 300 mV/s in 2 mL of detection solution (containing 18 mmol/L triethylamine, pH 7.4), respectively. The ECL biosensor was constructed according to the successive assembly of (i) the Zr-TCPE as ECL material, (ii) silver nanoparticles (Ag NPs) as immobilization matrix of concanavalin A (Con A) and (iii) the Con A as a cells trapping agent, which achieved the in situ monitoring of hydrogen peroxide (H₂O₂) released from the tumor cells under the stimulative effect of phorbol 12-myristate 13-acetate (PMA). Furthermore, the ECL biosensor could rapidly distinguish cancer cells from normal cells. What is more, the ECL biosensor is also suitable for the detection of H₂O₂ released from the various tumor cells. The prepared Zr-TCPE, as the combination of strong ECL emission, easy preparation and good biocompatibility, was expected to be a kind of popular luminophors for the clinical detection of tumor cells.

Key words: metal-organic framework material, 1,1,2,2-tetrachlorophenol(4-carboxylic benzene)ethylene, ECL biosensor, tumor cell, hydrogen peroxide

引用此文

廖妮, 钟霞, 梁文斌, 袁若, 卓颖. ECL金属-有机框架(MOF)生物传感平台用于肿瘤细胞分泌H₂O₂的测定[J]. 化学学报, 2021, 79(10): 1257-1264.

Ni Liao, Xia Zhong, Wen-Bin Liang, Ruo Yuan, Ying Zhuo. Metal-organic Frameworks (MOF)-based Novel Electrochemiluminescence Biosensing Platform for Quantification of H₂O₂ Releasing from Tumor Cells[J]. Acta Chimica Sinica, 2021, 79(10): 1257-1264.

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图/表 6

图1. Zr-TCPE的合成示意图(A), 基于Zr-TCPE的ECL传感器构建(B)及传感器对H2O2的响应机理(C)

Figure 1. The schematic diagram of the preparation of Zr-TCPE (A), the fabrication procedure of Zr-TCPE based ECL biosensor (B) and the possible response mechanism of the biosensor for H2O2 (C)

图2. Zr-TCPE的SEM图(A)及Zr-TCPE中C, O和Zr元素的SEM-EDX图(B). 配体H4TCPE (a)和Zr-TCPE (b)的FT-IR光谱(C)及Zr-TCPE的XRD谱(D)

Figure 2. SEM image of Zr-TCPE (A) and the SEM-EDX elemental mapping of C, O and Zr in Zr-TCPE (B). FT-IR spectra of the H4TCPE ligands (a) and Zr-TCPE (b) (C), and XRD pattern of Zr-TCPE (D)

图3. (A)不同浓度Zr-TCPE溶液的荧光照片, 从左往右Zr-TCPE的浓度依次为: 0 mg/mL, 10-4 mg/mL, 10-3 mg/mL, 10-2 mg/mL, 10-1 mg/mL, 1 mg/mL. Zr-TCPE在日光灯(B)和紫外灯(C)照射下的照片. (D) H4TCPE单体(a)和Zr-TCPE (b)的荧光发射谱. (E) Zr-TCPE的ECL光谱图. (F) Zr-TCPE的ECL光谱热图

Figure 3. (A) FL photographs of the Zr-TCPE solution with different concentrations, the concentrations: 0 mg/mL, 10-4 mg/mL, 10-3 mg/mL, 10-2 mg/mL, 10-1 mg/mL, 1 mg/mL (from left to right). The corresponding FL photographs of the Zr-TCPE under natural sunlight (B) and 365 nm UV lamp (C). (D) The FL spectra of H4TCPE monomer (a) and Zr-TCPE (b), respectively. The ECL spectra (E) and heat map (F) of the Zr-TCPE

图4. (A)不同电极的DPV曲线. (a)裸GCE和(b) Zr-TCPE/GCE在PBS中; (c) Zr-TCPE/GCE在N2饱和的PBS中. (B) Zr-TCPE/GCE在不同电位范围下的脉冲曲线, 检测底液为含有18 mmol/L TEA的PBS. (C) H4TCPE在不同状态下的ECL响应曲线. (a) GCE在含有2.75 mmol/L H4TCPE单体、18 mmol/L TEA和0.1 mol/L的(TBA)BF4的乙腈溶液中, (b) H4TCPE微纳晶体/GCE和(c) Zr-TCPE/GCE在含有18 mmol/L TEA的PBS中. 扫描速度: 300 mV/s. (D) H4TCPE微纳晶体(a)和Zr-TCPE (b)的ECL光谱图

Figure 4. (A) The DPV curves of different electrodes. (a) Bare GCE and (b) Zr-TCPE/GCE in the PBS, (c) Zr-TCPE/GCE in N2-saturated PBS. (B) ECL transients of Zr-TCPE/GCE in PBS containing 18 mmol/L TEA under different potentials. (C) ECL response curves of H4TCPE under different states. (a) The bare GCE in acetonitrile solution containing 2.75 mmol/L H4TCPE, 18 mmol/L TEA and 0.1 mol/L (TBA)BF4, (b) TCPE crystals/GCE and (c) Zr-TCPE/GCE in PBS containing 18 mmol/L TEA. Scan rates: 300 mV/s. (D) The maximum ECL spectra of TCPE crystals (a) and Zr-TCPE (b)

图5. (A)不同修饰电极在不同的检测底液中的ECL响应曲线. (a)裸GCE在PBS中, (b) Zr-TCPE/GCE在含有18 mmol/L TEA的PBS中, (c) Zr-TCPE/GCE在含有18 mmol/L的TEA和1 μg/mL PMA的PBS中, (d) Zr-TCPE/GCE在含有18 mmol/L的TEA, 1 μg/mL PMA和5 μmol/L H2O2的PBS中. (B)构建的生物传感器(Con A/Ag NPs/Zr-TCPE/GCE)孵育不同浓度Hela细胞的ECL响应

Figure 5. (A) ECL-time curves of the different modified electrodes in different detection solution. (a) Bare GCE in PBS, (b) Zr-TCPE/GCE in PBS containing 18 mmol/L TEA, (c) Zr-TCPE/GCE in PBS containing 18 mmol/L TEA and 1 μg/mL PMA, (d) Zr-TCPE/GCE in PBS containing 18 mmol/L TEA, 1 μg/mL PMA and 5 μmol/L H2O2. (B) ECL responses of the proposed biosensor (Con A/Ag NPs/Zr-TCPE/GCE) to Hela cells at different concentrations

图6. (A) Hela细胞与不同浓度的Zr-TCPE孵育48 h后的存活率. (B) Zr-TCPE/GCE在检测底液(含有18 mmol/L的TEA的PBS)含有不同物质条件下的ECL-电位曲线. (a)检测底液在N2饱和的条件下, (b)检测底液在空气饱和的条件下, (c)检测底液含有5 μmol/L H2O2, (d)检测底液含有0.5%二甲基亚砜和5 μmol/L H2O2, (e)检测底液含有4.3 mmol/L对苯醌和5 μmol/L H2O2

Figure 6. (A) The viability of the Hela cells after incubated with Zr-TCPE with different concentrations for 48 h. (B) The ECL-potential curves of Zr-TCPE/GCE in detection solution (PBS containing 18 mmol/L TEA) containing different substances. (a) N2-saturated detection solution, (b) air-saturated detection solution, (c) detection solution containing 5 μmol/L H2O2, (d) detection solution containing 0.5% DMSO and 5 μmol/L H2O2, (e) detection solution containing 4.3 mmol/L p-benzoquinone and 5 μmol/L H2O2

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ECL金属-有机框架(MOF)生物传感平台用于肿瘤细胞分泌H₂O₂的测定

Metal-organic Frameworks (MOF)-based Novel Electrochemiluminescence Biosensing Platform for Quantification of H₂O₂ Releasing from Tumor Cells

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