One-Step Detection of RNA in Small Extracellular Vesicles from Plasma for Diseases Diagnosis by a Multisatellites@planets Molecular Imprinting Platform

RNA in small extracellular vesicles (sEVs) from plasma is a reliable biomarker for disease diagnosis. However, the cumbersome steps and operator dependency for extraction and analysis of sEVs RNA in plasma have limited their application. Here, we developed a multisatellites@planets molecular imprinting detection platform for sEVs capture and RNA analyzation in a one-step process directly from a small amount of plasma. In this platform, magnetic beads as "planet" templates were utilized for size recognition of sEVs, and Au nanoparticles as "multi-satellites" templates were used to immobilize liposome probes for sEVs grasp and RNA detection through membrane fusion. As for the detection accuracy, the results from our platform demonstrate a high level of concordance with qRT-PCR (R² value of 0.9937). Moreover, we successfully used 10 μL of plasma to analyze sEVs RNA, effectively differentiating healthy donors and lung cancer patients with an accuracy of 91.18% (combined MALAT1 and miR-21). This novel platform provides a pretreatment-free, user-friendly, highly accurate, and sensitive strategy for detecting the RNA of sEVs in plasma, indicating its potential capability for disease diagnosis.