DNA Logic Operations in Living Cells Utilizing Lysosome-Recognizing Framework Nucleic Acid Nanodevices for Subcellular Imaging

DNA logic nanodevices that in situ operate within living cells have attracted increasing interest and shown great promise for gene regulation and target recognition. A challenge remains how to control their activation inside specific cellular compartments. Toward this goal, here we report a lysosome-recognizing framework nucleic acid (FNA) nanodevice using an i-motif and an ATP-binding aptamer (ABA) incorporated into a DNA triangular prism (DTP) as the logic-controlling units. Once entering the lysosomal compartments, the FNA device responds to lysosomal pH and ATP via the folding of i-motif and ABA, which triggers a structural change of FNA and the release of a reporter structure for subcellular imaging. With endogenous proton and ATP as two inputs, an AND logic gate is built and in situ operated within living lysosomes by pH and ATP modulation with external drug stimuli. Given the abnormal levels of pH and ATP within some cancer cells or dysfunctional lysosomal cells, in this context our designed FNA logic device may find extended applications in controllable drug release and disease treatment.