Ultrasensitive electrochemiluminescence biosensor for the detection of tumor exosomes based on peptide recognition and luminol-AuNPs@g-CN nanoprobe signal amplification.

Highly sensitive determination of tumor exosomes is significant for early diagnosis of cancers and precision therapy. Herein, a sandwich peptide-based electrochemiluminescence (ECL) biosensor was developed for determination of phosphatidylserine (PS)-positive exosomes, a promising biomarker for early diagnosis of ovarian malignancy. A PS-specific binding peptide with high affinity was immobilized on Au nanoflowers (AuNFs) modified biosensing interface for recognition and capture of exosomes. Meanwhile, g-CN nanosheet loaded with luminol capped AuNPs (Lum-AuNPs@g-CN) nanocomposite was used as the ECL signal nanoprobe. The g-CN nanosheets with large surface area were not only utilized as the carrier to immobilize more peptides for recognition of exosomes but also used to catalyze co-reactant HO decomposition to achieve the ECL signal amplification of luminol-HO system. Under optimal conditions, the biosensor showed superior performances compared with most currently available methods, including wider linear range across 5 orders of magnitude and a lower detection limit (LOD) down to 39 particles μL. Moreover, the biosensor could be applicable for determination of exosomes in complex biological samples. This study indicates the combination of peptide recognition with nanoprobe as a label for signal amplification in sandwich ECL biosensing is a great promising strategy for sensitive and cost-effective determination of exosomes.