Dual Gatekeepers-Driven Signal Amplification Strategy for Precise Detection and Modulation of Ovarian Cancer Exosome Subtypes

Early detection of ovarian cancer remains a significant challenge due to the lack of symptoms in its early stages and the overlap in protein expression patterns between malignant and benign conditions. In this study, we introduce a dual gatekeepers-driven signal amplification strategy for the highly sensitive detection and precise modulation of ovarian cancer-derived exosome subtypes. By employing CA125 and carcinoembryonic antigen (CEA) aptamers as dual gatekeepers, this strategy selectively activates functional regions on exosome membranes, triggering the opening of hairpin DNA structures (HP) upon recognition of specific protein patterns. The opened HP then initiate an exonuclease III-powered DNA walking system and nucleic acid-stabilized Ag⁰ nanoclusters (AgNCs), significantly amplifying the detection sensitivity. This approach not only enables the specific differentiation of malignant exosomes from benign ones but also facilitates the distinction between early and late-stage tumors. Moreover, it regulates the interaction between ovarian cancer-derived exosomes and target cells, promoting the exchange of biological information and material transfer. This innovative strategy serves as a powerful tool for early tumor detection while offering valuable insights into the interactions between exosome subtypes and tumor cells. Its application establishes a strong theoretical foundation for investigating the roles of exosomes in intercellular communication, immune evasion, and other biological processes, with far-reaching implications for cancer immunotherapy and related research.