An endogenous activation-controlled DNA tetrahedron nanoreactor with spatial confinement for ultra-sensitive detection of miR-200c in living cells

High-precision detection and imaging of cancer-related miRNAs in living cells play a crucial role in early tumor diagnosis and prognosis. However, the primary challenge lies in developing a method that can achieve both high precision and rapid detection to improve detection efficiency. To tackle this challenge, we employed the spatial confinement effect to construct an enzyme-controlled DNA Tetrahedron nanoreactor (E-TDN-EDC) for highly specific and rapid detection of miRNAs in tumor cells. By confining reactants within a compact space to increase collision efficiency, thereby accelerating reaction kinetics. Endogenous enzyme activation can precisely distinguish between tumor cells from normal cells, achieving specific imaging of miRNAs in tumor cells. TDN nanoreactor have robust biostability, excellent specificity and rapid reaction kinetics. It is noted that due to the spatial confinement effect and the design of endogenous enzyme-activated nanoprobes, the detection limit of E-TDN-EDC was as low as 0.89 pM, and rapidly imaging in living cells can be achieved within 70 min. Consequently, this approach holds significant promise for the early diagnosis of tumors and efficient, accurate postoperative assessment. • Developed an ultra-sensitive nanoprobe for detection of miRNA in tumor cells. • Enzyme-controlled DNA amplification circuit achieve specific imaging of miRNA. • The unique tetrahedron structure enhanced detection efficiency and biostability.