2. Academic Validation
  3. Simultaneous detection of cancerous exosomal miRNA-21 and PD-L1 with a sensitive dual-cycling nanoprobe

Simultaneous detection of cancerous exosomal miRNA-21 and PD-L1 with a sensitive dual-cycling nanoprobe

  • Biosens Bioelectron. 2022 Nov 15;216:114636. doi: 10.1016/j.bios.2022.114636.
Xiaoling Qin 1,  Yuanhang Xiang 1,  Na Li 1,  Binqi Wei 1,  Yu Chen 1,  Dan Fang 1,  Min Fang 2,  Qiaofeng Li 1,  Jia Liu 3,  Yujin Tang 3,  Xinchun Li 1,  Fan Yang 4
Affiliations

Affiliations

  • 1 Key Laboratory of Micro-Nanoscale Bioanalysis and Drug Screening of Guangxi Higher Education, Guangxi Beibu Gulf Marine Biomedicine Precision Development and High-Value Utilization Engineering Research Center, National Center for International Research of Bio-targeting Theranostics, School of Pharmacy, Guangxi Medical University, Nanning, 530021, China.
  • 2 Department of Clinical Laboratory, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, China.
  • 3 Guangxi Key Laboratory of Basic and Translational Research of Bone and Joint Degenerative Diseases, Department of Orthopedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, China.
  • 4 Key Laboratory of Micro-Nanoscale Bioanalysis and Drug Screening of Guangxi Higher Education, Guangxi Beibu Gulf Marine Biomedicine Precision Development and High-Value Utilization Engineering Research Center, National Center for International Research of Bio-targeting Theranostics, School of Pharmacy, Guangxi Medical University, Nanning, 530021, China. Electronic address: yangfan@gxmu.edu.cn.
PMID: 35986985 DOI: 10.1016/j.bios.2022.114636
Abstract

Simultaneous detection of specific exosomal surface proteins and inner MicroRNAs are hampered by their heterogeneity, low abundance and spatial segregation in nanovesicles. Here, we design a dual-cycling nanoprobe (DCNP) to enable single-step simultaneous quantitation of cancerous exosomal surface programmed death-ligand 1 (PD-L1) (ExoPD-L1) and miRNA-21 (ExomiR-21) directly in exosome lysates, without resorting to either RNA extraction or time-consuming transmembrane penetration. In this design, DNA molecular machine-based dual-recognition probes co-assemble onto gold nanoparticle surface for engineering 'silent' DCNPs, which enable signal-amplified synchronous response to dual-targets as activated by ExomiR-21 and ExoPD-L1 within 20 min. Benefiting from cycling amplification of the molecular machine, DCNPs sensor achieves detection limits of tumor exosomes, ExoPD-L1 and ExomiR-21 down to 10 particles/μL, 0.17 pg/mL and 66 fM, respectively. Such a sensitive dual-response strategy allows simultaneous tracking the dynamic changes of ExoPD-L1 and ExomiR-21 expression regulated by signaling molecules or therapeutics. This approach further detects circulating ExoPD-L1 and ExomiR-21 in human plasma to differentiate breast Cancer patients from healthy individuals with high accuracy, showing great potential of DCNPs for simultaneous profiling exosomal surface and inside biomarkers, and for clinical precision diagnosis.

Keywords

DNA molecular Machine; Dual-cycling nanoprobe; Exosomal miRNA; PD-L1; Simultaneous detection.

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