A dual “turn-on” biosensor based on AIE effect and FRET for in situ detection of miR-125b biomarker in early Alzheimer's disease

Qin Zhang, Bohan Yin, Yingying Huang, Yutian Gu, Jiaxiang Yan, Jiareng Chen, Chuanqi Li, Yu Zhang, Siu Hong Dexter Wong, Mo Yang

Research output: Journal article publicationJournal articleAcademic researchpeer-review

28 Citations (Scopus)

Abstract

MicroRNA-125b (miR-125b) is highly associated with synaptic dysfunction and tau hyperphosphorylation in the early pathogenesis of Alzheimer's disease (AD), making it a promising biomarker for early AD diagnosis. Hence, there is an urgent need for a reliable sensing platform to assist in situ miR-125b detection. In this work, we report a dual “turn-on” fluorescence biosensor based on the nanocomposite of aggregation-induced emission fluorogen (AIEgen)-labeled oligonucleotide (TPET-DNA) probes immobilized on the surface of cationic dextran modified molybdenum disulfide (TPET-DNA@Dex-MoS2). In the presence of the target, TEPT-DNA can hybridize with miR-125b to form a DNA/RNA duplex, causing TPET-DNA to detach from the surface of Dex-MoS2 that simultaneously activates the dual fluorescence enhancement processes: (1) recovery of TPET-DNA signal and (2) strong fluorescent emission from AIEgen triggered by restriction of the intramolecular rotation. The sensing performance of TPET-DNA@Dex-MoS2 was demonstrated by detecting miR-125b in vitro with good sensitivity at the picomolar level and rapid response (≤1 h) without amplification procedures. Furthermore, our nanoprobes exhibited excellent imaging capabilities to aid real-time monitoring of the endogenous miR-125b in PC12 cells and brain tissues of mice AD model induced by local administration of okadaic acid (OA). The fluorescence signals of the nanoprobes indicated miR-125b was spatially associated with phosphorylated tau protein (p-tau) in vitro and in vivo. Therefore, TPET-DNA@Dex-MoS2 could be a promising tool for in situ and real-time monitoring of the AD-related microRNAs and also provide mechanistic insight into the early prognosis of AD.

Original languageEnglish
Article number115270
JournalBiosensors and Bioelectronics
Volume230
DOIs
Publication statusPublished - 15 Jun 2023

Keywords

  • Aggregation-induced emission (AIE) fluorogens
  • Alzheimer's disease
  • microRNA detection
  • Molybdenum disulfide (MoS)

ASJC Scopus subject areas

  • Biotechnology
  • Biophysics
  • Biomedical Engineering
  • Electrochemistry

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