Proximity labeling-assisted click conjugation for electrochemical analysis of specific subpopulations in circulating extracellular vesicles

  • Biosens Bioelectron. 2024 Jul 1:255:116245. doi: 10.1016/j.bios.2024.116245.
Yue Cao  1 ,  Liang Zhou  2 ,  Guozhang Zhou  1 ,  Wensheng Liu  3 ,  Haiyan Cui  4 ,  Ya Cao  5 ,  Xiaolei Zuo  6 ,  Jing Zhao  7
Affiliations
  • 1. Center for Molecular Recognition and Biosensing, Shanghai Engineering Research Center of Organ Repair, School of Life Sciences, Shanghai University, Shanghai, 200444, China; Joint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education), Shanghai University, Shanghai, 200444, China.
  • 2. Center for Molecular Recognition and Biosensing, Shanghai Engineering Research Center of Organ Repair, School of Life Sciences, Shanghai University, Shanghai, 200444, China; Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
  • 3. Department of Gastroenterology, Dongying People's Hospital, Dongying, 257091, China.
  • 4. Shanghai Clinical Research Center for Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, 200433, China.
  • 5. Center for Molecular Recognition and Biosensing, Shanghai Engineering Research Center of Organ Repair, School of Life Sciences, Shanghai University, Shanghai, 200444, China; Joint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education), Shanghai University, Shanghai, 200444, China. Electronic address: [email protected].
  • 6. Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China. Electronic address: [email protected].
  • 7. Center for Molecular Recognition and Biosensing, Shanghai Engineering Research Center of Organ Repair, School of Life Sciences, Shanghai University, Shanghai, 200444, China; Joint International Research Laboratory of Biomaterials and Biotechnology in Organ Repair (Ministry of Education), Shanghai University, Shanghai, 200444, China. Electronic address: [email protected].
PMID: 38555770 DOI: 10.1016/j.bios.2024.116245
Abstract

Sensitive and accurate analysis of specific subpopulations in circulating extracellular vesicles (EVs) can provide a wealth of information for Cancer diagnosis and management. Thus, we propose herein a new electrochemical biosensing method based on a proximity labeling-assisted click conjugation strategy. The method's core design is use of antibody-guided proximity labeling to equip target EVs with a large amount of alkyne groups, so that azide-tagged silver nanoparticles can be accurately loaded onto target EV surfaces, via click conjugation, to generate significant electrochemical responses. Adopting CD44-positive EVs as the model, the electrochemical method was demonstrated by analyzing target EVs across a wide linear range (103-109 particles/mL) with acceptable sensitivity and specificity. Satisfactory utility in clinical blood samples, and versatility with human epidermal growth factor receptor-2-positive EVs as alternative targets, were also shown. This method may thus provide a novel approach to specific subgroup analyses of circulating EVs, and is expected to offer reliable guidance for Cancer diagnoses and management strategies.

Keywords
Click chemistry; Electrochemical biosensing; Extracellular vesicles; Liquid biopsy; Proximity labeling.
Products