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An aptamer based fluorometric assay for amyloid-β oligomers using a metal-organic framework of type Ru@MIL-101(Al) and enzyme-assisted recycling

Abstract

Amyloid-beta (Aβ) oligomers causing neuron damage are regarded as potential therapeutic targets and diagnostic markers for Alzheimer’s disease (AD). A homogeneous turn-on fluorometric aptasensor is described for Aβ oligomers. It is highly selective and non-invasive and based on (a) the use of a luminescent metal-organic framework carrying aptamer-modified AuNPs (L-MOF/Apt-Au) as tracking agent, and (b) enzyme-assisted target recycling signal amplification. The tracking agent does not emit fluoresce by fluorescence resonance energy transfer (FRET) between the luminescent MOF as donor and Apt-Au as the acceptor under the excitation wavelength of 466 nm. When Aβ oligomers are added to the tracking agent solution, the Apt-Au on tracking agent can preferentially bind with Aβ oligomers and then be released. This turns the “off” signal of the luminescent MOF tracer to the “on” state. The enzyme (Rec Jf exonuclease) added into the supernatant further improves sensitivity due to enzyme-assisted target-recycling signal amplification. The assay has an excellent linear response to Aβ oligomers from 1.0 pM to 10 nM, with a detection limit of 0.3 pM. This homogeneous turn-on fluorometric method is expected to have potential and applications in clinical diagnosis.

Schematic representation of fluorometric assay for amyloid-β oligomers based on luminescence metal-organic framework nanocomposites as tracking agent with exonuclease-assisted target recycling.

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Acknowledgements

This work was financially supported by 2018 Academic New Seedling Cultivation and Innovation Exploration Project of Guizhou Provincial Science and Technology Department (No. [2018]5784-05), and Ph. D. Foundation of Zunyi Normal College (No. BS[2019]10).

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Correspondence to Hong-Xia Ren.

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Ren, H., Miao, Y. & Zhang, Y. An aptamer based fluorometric assay for amyloid-β oligomers using a metal-organic framework of type Ru@MIL-101(Al) and enzyme-assisted recycling. Microchim Acta 187, 114 (2020) doi:10.1007/s00604-019-4092-3

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Keywords

  • Luminescent metal-organic framework
  • Enzyme assisted target recycling
  • Tracking agent
  • Homogeneous assay
  • Turn-on fluorometry