Facilitating In Situ Tumor Imaging with a Tetrahedral DNA Framework‐Enhanced Hybridization Chain Reaction Probe

Abstract Rapid and efficient tools for early cancer detection have diagnostic and therapeutic value. Given that the DNA hairpin‐based hybridization chain reaction (HCR) is effective in detecting various biological targets, a tetrahedral framework DNA‐enhanced (TDN‐enhanced) HCR detection system (T‐probe system) is introduced for cancer‐related targets and its versatility is demonstrated by detecting intracellular target miRNA 21 and cellular membrane target nucleolin. Benefiting from the spatial confinement of the TDN, the T‐probe system demonstrates a high detection rate. It increases the reaction efficiency of nude hairpins in vitro while accurately and rapidly recognizing both membrane and intracellular cancer‐related targets in living cells. Furthermore, it exhibits superior fluorescence in vivo within 15 s of peripheral‐tumor injection and 10 min of tail‐vein injection. The T‐probe system efficiently and accurately images tumor‐related biomarkers in vitro and in vivo, thereby demonstrating great potential for clinical diagnosis and therapeutic applications.