微升体积脑脊液样品中ZIF-8微游泳者自我快速动态破坏:对淀粉样变的选择性评估。

IF 6.7 1区 化学 Q1 CHEMISTRY, ANALYTICAL
Javier Bujalance-Fernández, Eva Carro, Desiree Antequera, Beatriz Jurado-Sánchez* and Alberto Escarpa*, 
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引用次数: 0

摘要

在此,我们描述了磁性沸石咪唑框架(ZIF-8)微游泳体的合成,用于检测和定量脑脊液(CSF)样品中的淀粉样蛋白(a β1-42)肽,该肽被用作诊断阿尔茨海默病(AD)的淀粉样变性的生物标志物。采用磁性Fe3O4纳米粒子对ZIF-8进行外部修饰,将奎宁作为荧光探针后内包封制备微游泳体。对微游泳器的磁性和表面性质进行了微调,以获得具有负载荧光探针和外部磁性发动机的内部多孔结构的定制结构。对于奎宁的封装,大孔结构优于微孔结构,可将负载效率提高约50%,并且还允许铁氧体的外部修饰以赋予微游泳者所需的磁性能。检测原理依赖于a β1-42肽结构中氨基酸靶序列对ZIF-8中Zn单元的特异性亲和力,导致微游泳体自毁,随后以浓度依赖的方式释放奎宁。使用无生物受体的磁辅助微池可以在仅10 μL的脑脊液样品中直接评估a β1-42肽,仅需10分钟。具有出色的分析性能,检测限为40 pg/mL,线性范围为140至1200 pg/mL (r = 0.9990),涵盖了临床实践的范围。对Aβ1-42肽也获得了极好的选择性,它接近于对人脑淀粉样变性的极好评估,正如在诊断的脑脊液样本中,我们的微游泳方法获得的定量水平与酶联免疫吸附法相比获得的良好相关性(r = 0.97)所证明的那样,Tau蛋白也因与Aβ1-42肽共存而被测定。由于脑脊液生物标志物是目前唯一临床验证的AD生物流体诊断测试,我们的方法将大大减少测定Aβ水平所需的体积,减少临床实践中腰椎穿刺副作用的影响。它成为一种新的无生物受体的方法,更容易、侵入性更小地测量脑脊液中的a β1-42肽,成为患者一生中间接预测脑组织淀粉样变的有价值的工具,为AD的早期治疗开辟了可能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
ZIF-8 Microswimmers Self-Fast Dynamic Destruction in Microliter Volumes of Cerebrospinal Fluid Samples: Toward a Selective Assessment of Amyloidosis

Herein, we describe the synthesis of magnetic zeolitic imidazole framework (ZIF-8) microswimmers for detecting and quantifying the amyloid beta (Aβ1–42) peptide in cerebrospinal fluid (CSF) samples, which are used as a biomarker of amyloidosis for diagnosing Alzheimer’s disease (AD). The microswimmers are prepared by external decoration of the ZIF-8 with magnetic Fe3O4 nanoparticles, followed by post internal encapsulation of quinine as fluorescent probe. The magnetic and surface properties of the microswimmers are fine-tuned to obtain tailored structures with an inner porous structure with the loaded fluorescent probe and outer magnetic engines. A macroporous structure was preferred over a microporous structure for quinine encapsulation, increasing the loading efficiency by about 50%, allowing also external decoration of the ferrite to impart the desired magnetic properties to the microswimmer. The principle for detection relies on the specific affinity of target sequence of amino acids in the Aβ1–42 peptide structure toward the Zn units in the ZIF-8, resulting in the self-destruction of the microswimmers and subsequent release of quinine in a concentration-dependent manner. The use of the bioreceptor-free magnetic assisted microswimmers allows for direct assessment of Aβ1–42 peptide in only 10 μL of CSF samples in just 10 min. Excellent analytical performance with a limit of detection of 40 pg/mL and a linear range ranging from 140 to 1200 pg/mL (r = 0.9990), covering the range in the clinical practice, is obtained. An excellent selectivity was also obtained toward the Aβ1–42 peptide which approaches an excellent assessment of amyloidosis in the human brain, as demonstrated by the good correlation obtained (r = 0.97) between the quantitative levels obtained in our microswimmers approach in comparison with the enzyme-linked immunosorbent assay method in diagnosed CSF samples from patients where Tau protein was also determined due to its coexistence with Aβ1–42 peptides. Since CSF biomarkers are currently the only clinically validated biofluid diagnostic test for AD, our approach will drastically reduce the volume required to determine Aβ levels, reducing the impact of the side effects of lumbar puncture in clinical practice. It became a novel bioreceptor-free approach to more easily, less invasively measure Aβ1–42 peptide in CSF, becoming a valuable tool for indirect amyloidosis prediction in brain tissues in the patient’s lifetime, opening the possibility for early treatment of the AD.

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来源期刊
Analytical Chemistry
Analytical Chemistry 化学-分析化学
CiteScore
12.10
自引率
12.20%
发文量
1949
审稿时长
1.4 months
期刊介绍: Analytical Chemistry, a peer-reviewed research journal, focuses on disseminating new and original knowledge across all branches of analytical chemistry. Fundamental articles may explore general principles of chemical measurement science and need not directly address existing or potential analytical methodology. They can be entirely theoretical or report experimental results. Contributions may cover various phases of analytical operations, including sampling, bioanalysis, electrochemistry, mass spectrometry, microscale and nanoscale systems, environmental analysis, separations, spectroscopy, chemical reactions and selectivity, instrumentation, imaging, surface analysis, and data processing. Papers discussing known analytical methods should present a significant, original application of the method, a notable improvement, or results on an important analyte.
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