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

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.