DNA sensor-engineered nanovesicles for multi-logic-cascaded signal-amplified miRNA imaging

The low abundance of tumor-related miRNA and significant background signal interference highlight the necessity for sensitive and accurate miRNA imaging. Herein, we report the DNA sensor-engineered nanovesicles that achieve sensitive and accurate imaging of target miRNA-21 by combining multi-logic-cascaded response strategy with catalytic hairpin assembly (CHA)-based signal amplification strategy. The DNA sensor was constructed by the glutathione (GSH)-responsive sequence, target recognition sequence, CHA hairpins and a DNA bridge sequence. Co-existence of GSH and target miRNA-21 could trigger disulfide bond cleavage, subsequently following the target-mediated CHA cycling. The sensor was tested in buffers showing dynamic ranges of 10 pM to 1 nM for miRNA-21 with a detection limit of 3.9 pM. The surface of nanovesicles loaded with the DNA sensor was modified by folate (FA). This DNA sensor-engineered nanovesicles allows for exogenous FA-controlled tumor cell identification and endogenous GSH-activated target-induced signal amplification, resulting in significantly enhanced sensitivity and precision for target miRNA-21 imaging.