Integrating All-rounder TiO Accelerated Electrochemiluminescence with Dual-Quenching PDA@COF Probes for Sensitive Quantification and Protein Profiling of Tumorous Exosomes.

Exosomes have been perceived as promising biomarkers for noninvasive cancer diagnosis and treatment monitoring. However, the sensitive and accurate quantification and phenotyping of exosomes remains challenging. Herein, a versatile electrochemiluminescence (ECL) aptasensor was proposed for the sensitive analysis of tumorous exosomes. Specifically, a ternary nanohybrid (Ru-HAuTiO), by covalently linking ECL luminophore Ru(dcbpy) with gold nanoparticles (AuNPs)-decorated hollow urchin-like TiO (HTiO), was ingeniously designed as a highly luminescent and self-enhanced ECL nanoemitter. Notably, the porous HTiO played an "all-rounder" role, including the carrier for ECL luminophores and AuNPs, coreaction accelerator, and specific exosome capturing scaffold through Ti-phosphate coordination interaction. On the other hand, a polydopamine modified covalent organic framework (PDA@COF) was employed as a quencher to remarkably attenuate the ECL of Ru-HAuTiO through a dual-quenching mechanism, and further labeled with a specific aptamer (Apt) of exosomal surface protein. Based on forming a Ru-HAuTiO/exosome/Apt-PDA@COF sandwich structure on the electrode, a "signal on-off" ECL platform for tumorous exosomes was constructed, realizing sensitive detection within the range of 3.1 × 10 particles/mL to 1 × 10 particles/mL and a low limit of detection of 1.41 × 10 particles/mL, achieving phenotypic profiling of surface proteins on different tumorous exosomes. This work provides a promising alternative method for the detection and analysis of exosomes.