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 10 3 to 10 10 particles mL −1 , 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. Precise assessment of lung cancer-derived exosomes is achieved based on dual-labelled membrane interface. The application in clinical samples confirms that the method can not only discriminate lung cancer patients from healthy population but also achieve accurate tumor staging with respect to disease progression.