Detection of colorectal cancer-derived exosomes based on covalent organic frameworks

Covalent organic frameworks (COFs) have attracted more and more attention due to their diverse structures and multifunctionality. Their unique physicochemical properties make them exhibit great application potential in the field of biosensing. In this work, we have designed and fabricated a novel COFs-based nanoprobe named HRP-pSC₄-AuNPs@COFs, where spherical COFs are functionalized with para-sulfocalix [4] arene hydrate (pSC₄)-modified gold nanoparticles (AuNPs) and horseradish peroxidase (HRP). Then, we have applied it for the electrochemical detection of colorectal cancer (CRC)-derived exosomes. In this design, pSC₄ as amicable linker can recognize and bind with various amino acid residues on the exosomes surface, while AuNPs with excellent conductivity can accelerate the migration of charge carriers and improve the response of biosensors. Noteworthy, the high porosity of COFs allows them to load a large amount of HRP, endowing COF with high catalytic activity. Meanwhile, the exoskeleton of COFs can maintain the functionality of HRP with significantly elevated stability. With such design, the proposed method shows excellent analytical performance for the detection of CRC-derived exosomes in the linear range from 5 × 10² to 10⁷ particles/μL with a detection limit down to 160 particles/μL. Further, this method has also been used to analyze clinical serum sample, and can successfully distinguish CRC patients from healthy people, indicating the promising potential in clinical diagnosis.