Endogenous Enzyme-Activated Spatial Confinement DNA Nanowire with a Tumor Cell-Specific Response for High-Precision Imaging of the Tumor/Normal Cells Boundary

Abstract

Developing tumor cell-specific imaging approaches is essential for the clear delineation of tumor margins. However, traditional imaging approaches suffered from low reaction kinetics as well as limited tumor specificity resulting from their “always active” sensing mode, making it difficult to accurately depict tumor boundary. To address these limitations, we developed an endogenous enzyme-activated spatial confinement DNA nanowire probe (E-SCNW) with an enhanced tumor/normal cell discrimination ratio for high precision imaging of the tumor/normal cells boundary. The spatial confinement effect can improve reaction kinetics, and the endogenous enzyme-activation design can confine fluorescence response to the tumor cells region. Additionally, no additional cell delivery carriers were required during the cross of the cell membrane into the intracellular space. It is worth noting that benefiting from the spatial confinement effect and endogenous enzyme-activation design, the detection limit was decreased by nearly 25.6-fold and the tumor/normal cells discrimination ratio was enhanced by nearly 4.46-fold through using E-SCNW, indicating promising prospects in high-precision imaging of the tumor/normal cells boundary.