Surface plasmon resonance biosensor for exosome detection based on reformative tyramine signal amplification activated by molecular aptamer beacon

Journal of Nanobiotechnology

Zhiyang Li¹  Lin Liu²  Tao Wu²  Xiaolin Yu²  Wenqian Cheng³  Jia Li³  Xinmin Li³  Shijia Ding³  Huijie Bai³  Xinyu Li³  Wenqin Chen⁴ 

[1] Department of Clinical Laboratory, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 210008, Nanjing, China;Department of Laboratory Medicine, Zigong Fourth People’s Hospital, 643000, Sichuan, China;Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, 400016, Chongqing, China;Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, 400016, Chongqing, China;Department of Clinical Laboratory, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 210008, Nanjing, China;

关键词: HER2-positive exosomes;    Surface plasmon resonance;    Tyramine signal amplification;    G4-hemin;    Breast cancer diagnosis;   

DOI  :  10.1186/s12951-021-01210-x

来源: Springer

【 摘 要 】

Human epidermal growth factor receptor 2 (HER2)-positive exosomes play an extremely important role in the diagnosis and treatment options of breast cancers. Herein, based on the reformative tyramine signal amplification (TSA) enabled by molecular aptamer beacon (MAB) conversion, a label-free surface plasmon resonance (SPR) biosensor was proposed for highly sensitive and specific detection of HER2-positive exosomes. The exosomes were captured by the HER2 aptamer region of MAB immobilized on the chip surface, which enabled the exposure of the G-quadruplex DNA (G4 DNA) that could form peroxidase-like G4-hemin. In turn, the formed G4-hemin catalyzed the deposition of plentiful tyramine-coated gold nanoparticles (AuNPs-Ty) on the exosome membrane with the help of H2O2, generating a significantly enhanced SPR signal. In the reformative TSA system, the horseradish peroxidase (HRP) as a major component was replaced with nonenzymic G4-hemin, bypassing the defects of natural enzymes. Moreover, the dual-recognition of the surface proteins and lipid membrane of the desired exosomes endowed the sensing strategy with high specificity without the interruption of free proteins. As a result, this developed SPR biosensor exhibited a wide linear range from 1.0 × 104 to 1.0 × 107 particles/mL. Importantly, this strategy was able to accurately distinguish HER2-positive breast cancer patients from healthy individuals, exhibiting great potential clinical application.Graphical Abstract

【 授权许可】

CC BY