Dual-mode assay based on complementary scattering signals for accurate detection of exosomes derived from breast cancer

Detection of breast cancer-derived exosomes can help provide valuable information for the diagnosis of breast cancer. However, accurate detection of breast cancer exosomes remains challenging. Herein, taking SK-BR-3 exosome, a HER2-positive breast cancer exosome, as target model, a dual-mode assay based on complementary scattering signals for accurate detection of breast cancer-originated exosomes was constructed by proximity ligation mediated RCA reaction. To assure accuracy, three probes recognition (consisting of EpCAM, HER2, and MUC1 aptamers for the recognition of proteins on the surface of exosomes), proximity ligation reaction, and complementary scattering signals produced by the gold nanoparticles (Au NPs) in the supernatant and the magnetic beads-Au NPs (MBs-Au NPs) in the precipitate were used. This assay was equipped to distinguish HER2-positive breast cancer exosomes from HER2-negative and normal exosomes. Due to the RCA reaction triggered by proximity ligation, the dual-mode assay can detect SK-BR-3 exosome with a concentration of 1.0 × 102 particles/μL. With excellent accuracy and sensitivity, the assay can also distinguish healthy individuals from breast cancer patients, making it suitable for clinical application. This work was expected to provide an effective tool for accurate detection of breast cancer-derived exosomes.