Intracellular low-abundance microRNA imaging by a NIR-assisted entropy-driven DNA system

Intracellular microRNA (miRNA) imaging remains a key challenge due to its low abundance. Herein, we integrate a rationally designed elegant entropy-driven DNA probe with assisted DNA fuel on hollow copper sulfide nanoparticles (HCuSNPs) for intracellular miRNA imaging. The anchored assisted DNA fuel strand could be efficiently released by a NIR-II laser irradiation induced photothermal effect of the HCuSNPs. The DNA machine was activated by target miRNA binding and powered by NIR-responsive released DNA fuel through toehold-mediated strand displacement reactions, accomplished by strong fluorescence recovery. It demonstrated 2 orders of magnitude improvement in the detection sensitivity compared to molecular beacons (MBs). Reliable intracellular low-abundance miRNA imaging among different cells and monitoring of down-regulated miRNA was realized without external enzyme or fuel addition. Oncogenic miRNA imaging in vivo was also realized. The entropy-driven DNA machine system provides a facile and powerful tool for intracellular miRNA analysis and related biomedical applications.