An aptamer based fluorometric assay for amyloid-β oligomers using a metal-organic framework of typeRu@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-modifiedAuNPs (L-MOF/Apt-Au) as tracking agent, and (b) enzyme-assisted target recycling signal amplification. The tracking agent doesnot emit fluoresce by fluorescence resonance energy transfer (FRET) between theluminescent MOF as donor and Apt-Au as the acceptor under the excitation wavelength of 466nm. 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 theluminescent 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 anexcellent linear response to Aβ oligomers from 1.0pM to 10nM, with a detection limit of 0.3pM. This homogeneous turn-on fluorometric method is expected to have potential and applications in clinical diagnosis. Graphical abstractSchematic representation of fluorometric assay for amyloid-β oligomers based on luminescence metal-organic framework nanocomposites as tracking agent with exonuclease-assisted target recycling.