Ultrasensitive electrochemiluminescence biosensor for the detection of tumor exosomes

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-C₃N₄ nanosheet loaded with luminol capped AuNPs (Lum-AuNPs@g-C₃N₄) nanocomposite was used as the ECL signal nanoprobe. The g-C₃N₄ 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 H₂O₂ decomposition to achieve the ECL signal amplification of luminol-H₂O₂ 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⁻¹. 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.