Fluorescent Features and Applicable Biosensing of a Core-Shell Ag Nanocluster Shielded by a DNA Tetrahedral Nanocage

The DNA frame structure as a natural shell to stably shield the sequence-templated Ag nanocluster core (csAgNC) is intriguing yet challenging for applicable fluorescence biosensing, for which the elaborate programming of a cluster scaffold inside a DNA-based cage to guide csAgNC nucleation might be crucial. Herein, we report the first design of a symmetric tetrahedral DNA nanocage (TDC) that was self-assembled in a one-pot process using a C-rich csAgNC template strand and four single strands. Inside the as-constructed soft TDC architecture, the template sequence was logically bridged from one side to another, not in the same face, thereby guiding the in situ synthesis of emissive csAgNC. Because of the strong electron-repulsive capability of the negatively charged TDC, the as-formed csAgNC displayed significantly improved fluorescence stability and superb spectral behavior. By incorporating the recognizable modules of targeted microRNAs (miRNAs) in one vertex of the TDC, an updated TDC (uTDC) biosensing platform was established via the photoinduced electron transfer effect between the emissive csAgNC reporter and hemin/G-quadruplex (hG4) conjugate. Because of the target-interrupted csAgNC switching in three states with the spatial proximity and separation to hG4, an "on-off-on" fluorescing signal response was executed, thus achieving a wide linear range to miRNAs and a limit of detection down to picomoles. Without complicated chemical modifications, this simpler and more cost-effective strategy offered accurate cell imaging of miRNAs, further suggesting possible therapeutic applications.