Gene

Physics

Cancer

Biophysics

Aptamer

Molecular probe

Gene expression

Molecular biology

Nanotechnology

Organic chemistry

Nucleolus

Chemistry

Cytoplasm

Materials science

In vitro

In vivo

Nucleolin

Fluorescence in situ hybridization

In situ

Chromosome

Cancer research

Genetics

Biochemistry

Fluorescence-lifetime imaging microscopy

Quantum mechanics

Intracellular

In situ hybridization

Biology

Fluorescence

Cell biology

Cancer cell

Advanced Functional Materials

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.

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