Multivalency Interface and g-C3N4 Coated Liquid Metal Nanoprobe Signal Amplification for Sensitive Electrogenerated Chemiluminescence Detection of Exosomes and Their Surface Proteins.

Abstract

Exosomes derived vesicles and their surface anchored proteins by cells are extremely vital in intercellular communication, immuno-stimulation, and so on, which are promising in potential tumor biomarkers for disease diagnosis. However, the highly sensitive detection of exosomes and their surface proteins is still challenging. Herein, we combined the g-C3N4 conjugated polydopamine coated Galinstan liquid metal shell-core nanohybrids (g-C3N4@Galinstan-PDA) nanoprobes and multivalent PAMAM-AuNPs electrode interface to realize a highly sensitive detection of exosomes and their surface proteins by electrogenerated chemiluminescence (ECL) biosensor. The antibody-modified PAMAM-Au nanoparticles (NPs) electrode interface provided a multivalent recognition platform for highly effective capture of exosomes. Meanwhile, the Galinstan NPs were applied as the nanoprobe. The antibody modified g-C3N4@Galinstan-PDA can recognize the exosomes specifically and exhibit stable and strong ECL signals due to the excellent features of the Galinstan NPs in facilitating electron transfer and suppressing the g-C3N4 passivation during electrochemical reduction procedures. In this way, high sensitivity for HeLa cell derived exosomes analysis was obtained with the limit of detection (LOD) of 31 particles μL-1. Moreover, we operated the exosomes analysis in the real samples including serum, urine, and blood, and identified the multiple biomarkers (GPC1, CD9, CEA, and AFP) on the exosome surface derived from different kinds of cell lines (HeLa cell, OVCAR-3 cell, and BT474 cell). These consequences suggest that the proposed ECL biosensor has the potential to be a powerful tool for exosomes study and clinical diagnostic as well as wearable devices.