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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-MoS 2). 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-MoS 2 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-MoS 2 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-MoS 2 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. [Display omitted] [ABSTRACT FROM AUTHOR]

Upconversion nanoparticles (UCNPs) are ideal donors for luminescence resonance energy transfer (LRET)-based biosensors due to their excellent upconversion luminescence properties. However, the relatively large size of antibodies and proteins limits the application of UCNPs-based LRET biosensors in protein detection because the large steric hindrance of proteins leads to low energy transfer efficiency between UCNPs and receptors. Herein, we developed a magnetic responsive UCNPs-based LRET biosensor to control the coupling distance between antibody-functionalized UCNPs (Ab-UCNPs) as donors and antibody-PEG linker-magnetic gold nanoparticles (Ab-PEG-MGNs) as acceptors for ultrasensitive and highly selective detection of SARS-CoV-2 spike proteins. Our results showed that this platform reversibly shortened the coupling distance between UCNPs and MGNs and enhanced the LRET signal with a 10-fold increase in the limit of detection (LOD) from 20.6 pg/mL without magnetic modulation to 2.1 pg/mL with magnetic modulation within 1 h. The finite-difference time-domain (FDTD) simulation with cyclic distance change confirmed the distance-dependent LRET efficiency under magnetic modulation, which supported the experimental results. Moreover, the applications of this magnetic-responsive UCNP-based LRET biosensor could be extended to other large-size biomolecule detection. • Development of a magnetic-responsive upconversion luminescence resonance energy transfer (LRET) protein biosensor. • Magnetic modulation could overcome the space hindrance of protein to enhance energy tranfer efficiency. • A low limit of detection down to 2.1 pg/mL under magnetic modulation was achieved. • A rapid detection time within 40 min was achieved. [ABSTRACT FROM AUTHOR]