Precise assessment of lung cancer-derived exosomes based on dual-labelled membrane interface

Abstract

Lung cancer-derived exosomes are a kind of valuable and clinically-predictable biomarkers for lung cancer, but they have the limitations in individual differences when being applied in liquid biopsy. To improve their application value and accuracy in clinical diagnosis, a dual-labelled electrochemical method is herein reported for precise assessment of lung cancer-derived exosomes. To do so, two probes are prepared for the dual labeling of exosome membrane to run DNA assembly reactions: One is modified with cholesterol and can insert into exosome membrane through hydrophobic interaction; another one is linked with programmed death ligand-1 (PD-L1) antibody and can bind to exosome surface-expressing PD-L1 via specific immunoreaction. Quantum dots-tagged signal strands are used to collect respective DNA products, and produce stripping signals corresponding to the amounts of total exosome and surface-expressing PD-L1, respectively. A wide linear relationship is established for the quantitative determination of lung cancer-derived exosomes in the range from 10³ to 10¹⁰ particles/mL, whereas the ratiometric value of the two stripping signals is proven to have a better diagnostic use in screening and staging of lung cancer when being applied to clinical samples. Therefore, our method might provide a new insight into precise diagnosis of lung cancer, and offer sufficient information to reflect the biomarker level and guide the personalized treatment level even at an early stage in clinic.