Abstract

Amyloid-β peptide (Aβ) in serum is an effective biomarker for the early diagnosis of Alzheimer's disease (AD). However, there are serious challenges to monitor subtle changes of Aβ in the blood due to its low expression and the complex interference from the environment. Inspired by the delicate structure of natural enzymes, the metal site coordination, hydrophobic microenvironment, and the size selectivity feature, herein, a fluorescent probe based on bi-ligand zinc metal–organic frameworks is designed for accurate detection of Aβ in serum. By chelating with Zn2+, the fluorescent small molecule N-(6-(benzothiazol-2-yl)pyridin-3-yl)-5-(dimethylamino)naphthalene-1-sulfonamide (BPNS) participated in the self-assembly process as one of the organic linkers to form this novel flower-shaped probe Zn-FBIFs. As proposed, the synergism of hydrophobic nature and size-exclusion effect made Zn-FBIFs can rapidly and selectively enrich Aβ and exhibit excellent anti-interference ability towards interfering proteins in serum. Then by competitively binding to Zn2+, Aβ replaced the BPNS in Zn-FBIFs and the released BPNS gave a fluorescence signal for Aβ detection. The detection limit in undiluted serum was as low as 3.22 nM and that was two orders of magnitude decreased compared with the reported detection limit by BPNS calculated in 80-fold diluted serum. The results demonstrated our proposal of the bioinspired probe is effective in significantly improving the detection accuracy and that would give new insight into the development of novel probes for trace substance detection in complex biosamples.

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