TY - JOUR
T1 - A dual “turn-on” biosensor based on AIE effect and FRET for in situ detection of miR-125b biomarker in early Alzheimer's disease
AU - Zhang, Qin
AU - Yin, Bohan
AU - Huang, Yingying
AU - Gu, Yutian
AU - Yan, Jiaxiang
AU - Chen, Jiareng
AU - Li, Chuanqi
AU - Zhang, Yu
AU - Wong, Siu Hong Dexter
AU - Yang, Mo
N1 - Funding Information:
This work was supported by the Shenzhen Science and Technology Program-Basic Research Scheme ( JCYJ20220531090808020 ), the Research Grants Council (RGC) of Hong Kong Collaborative Research Grant ( C5078-21 EF ), the Research Grants Council (RGC) of Hong Kong General Research Grant ( PolyU 15217621 and PolyU 15210818 ), the Guangdong-Hong Kong Technology Cooperation Funding Scheme ( GHP/032/20SZ and SGDX20201103095404018 ), the Hong Kong Polytechnic University Shenzhen Institute Bai Cheng Bai Yuan Fund ( I2022A002 ), and the Hong Kong Polytechnic University Internal Fund ( 1-ZVVQ and 1-CD6J ). W.S.H.D. would like to acknowledge the start-up funding (1-ZVRY) from the Department of Biomedical Engineering and Start-up Fund for RAPs under the Strategic Hiring Scheme (1-BD8Q), the Hong Kong Polytechnic University (PolyU, University Grant Council), and PolyU Projects of RISports (1-CD5P) for supporting this work. This work was also supported by the University Research Facility in Life Sciences of the Hong Kong Polytechnic University .
Publisher Copyright:
© 2023 Elsevier B.V.
PY - 2023/6/15
Y1 - 2023/6/15
N2 - 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.
AB - 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.
KW - Aggregation-induced emission (AIE) fluorogens
KW - Alzheimer's disease
KW - microRNA detection
KW - Molybdenum disulfide (MoS)
UR - http://www.scopus.com/inward/record.url?scp=85151568112&partnerID=8YFLogxK
U2 - 10.1016/j.bios.2023.115270
DO - 10.1016/j.bios.2023.115270
M3 - Journal article
C2 - 37023551
AN - SCOPUS:85151568112
SN - 0956-5663
VL - 230
JO - Biosensors and Bioelectronics
JF - Biosensors and Bioelectronics
M1 - 115270
ER -