Abstract
Despite intense interest in design of DNAzyme sensors for molecular detection and imaging in living cells, their intracellular applications are still hampered by limited spatial control and poor bio-stability. Here we present controlled spatial confinement of a rationally designed, microRNA (miRNA)-activatable DNAzyme sensor probe (mDz) within the cavity of DNA nanocage, enabling efficient intracellular delivery with improved bio-stability for AND-gate molecular imaging. The mDz that possesses inactive DNAzyme activity is designed by the introduction of a blocking DNA strand, while miR-21 mediated strand displacement reaction allows for the formation of an intact DNAzyme structure for metal-ion-mediated catalytic reaction. Furthermore, the DNA nanocage serves as a nanocarrier for intracellular delivery of mDz, in which the cavity is accessible to the dual targets for logic-gated molecular imaging, while the confinement effect can provide steric protection of mDz by obstructing nuclease from entering the cavity of the DNA nanocage, resulting in enhanced bio-stability and improved molecular imaging precision. This strategy paves a way for the engineering of activatable DNA nanosensors with both self-delivery and self-protection capabilities to detect diverse intracellular targets.
Published Version
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