Preparation of covalent organic frameworks coated with cell membrane for precise analysis of cancer exosomes

Abstract

In this study, we have developed an electrochemical biosensor based on cell membrane-coated covalent organic framework (CM@COFs) for the selective detection of homologous exosomes. By integrating cell membrane-based biological recognition with enzyme-catalyzed electrochemical amplification, this biosensor may enable precise analysis of exosomes subtypes. In the design, CM@COFs achieve dual recognition functionality: the membrane selectively captures homologous exosomes, while the hairpin probe on the COF surface specifically hybridizes with miR-375. In the meantime, the encapsulated horseradish peroxidase (HRP) catalyzes the reduction of hydrogen peroxide, inducing 3,3',5,5'-tetramethylbenzidine (TMB) oxidation and producing an amplified electrochemical signal for quantitative analysis of the exosomes. The biosensor can achieve a detection limit as low as 27 particles/µL. Moreover, it can effectively differentiate serum samples from patients with triple-negative breast cancer (TNBC) and Luminal A breast cancer subtypes.