Integrating\nAll-rounder TiO<sub>2</sub> Accelerated\nElectrochemiluminescence with Dual-Quenching PDA@COF Probes for Sensitive\nQuantification and Protein Profiling of Tumorous Exosomes

Exosomes\nhave been perceived as promising biomarkers for noninvasive\ncancer diagnosis and treatment monitoring. However, the sensitive\nand accurate quantification and phenotyping of exosomes remains challenging.\nHerein, a versatile electrochemiluminescence (ECL) aptasensor was\nproposed for the sensitive analysis of tumorous exosomes. Specifically,\na ternary nanohybrid (Ru-HAuTiO<sub>2</sub>), by covalently linking\nECL luminophore Ru(dcbpy)<sub>3</sub><sup>2+</sup> with gold nanoparticles\n(AuNPs)-decorated hollow urchin-like TiO<sub>2</sub> (HTiO<sub>2</sub>), was ingeniously designed as a highly luminescent and self-enhanced\nECL nanoemitter. Notably, the porous HTiO<sub>2</sub> played an “all-rounder”\nrole, including the carrier for ECL luminophores and AuNPs, coreaction\naccelerator, and specific exosome capturing scaffold through Ti–phosphate\ncoordination interaction. On the other hand, a polydopamine modified\ncovalent organic framework (PDA@COF) was employed as a quencher to\nremarkably attenuate the ECL of Ru-HAuTiO<sub>2</sub> through a dual-quenching\nmechanism, and further labeled with a specific aptamer (Apt) of exosomal\nsurface protein. Based on forming a Ru-HAuTiO<sub>2</sub>/exosome/Apt-PDA@COF\nsandwich structure on the electrode, a “signal on–off”\nECL platform for tumorous exosomes was constructed, realizing sensitive\ndetection within the range of 3.1 × 10<sup>3</sup> particles/mL\nto 1 × 10<sup>8</sup> particles/mL and a low limit of detection\nof 1.41 × 10<sup>3</sup> particles/mL, achieving phenotypic profiling\nof surface proteins on different tumorous exosomes. This work provides\na promising alternative method for the detection and analysis of exosomes.