Ratiometric FRET Encoded Hierarchical ZrMOF @ Au Cluster for Ultrasensitive Quantifying MicroRNA In Vivo

Abstract Here, Zirconium metal−organic frameworks @ gold (ZrMOF @ Au) cluster architectures have been fabricated and then functionalized with two fluorescent dyes (Quasar [QS] and Cyanine5.5 [Cy5.5]) through deoxyribonucleic acid hybridization, to form a fluorescence resonance energy transfer (FRET) encoded ZrMOF @ Au‐QS/Cy5.5 complex. In the presence of the target intracellular microRNA (miR)‐21, the fluorescence of Cy5.5 at 705 nm (F 705 ) decreases and the fluorescence of QS at 665 nm (F 665 ) increases when Cy5.5 is released from the surface of ZrMOF @ Au‐QS/Cy5.5. The change in the fluorescence ratio (F 705 /F 665 ) shows an outstanding linear range of 0.006–67.9 amol/ng RNA , and the limit of detection is 4.51 zmol/ng RNA in living cells. The high ratio loading of nucleic acid on surface of ZrMOF @ Au cluster and two fluorescence encoded signal enables better sensitivity and reliability. Zeptomolar sensitivity and good linearity against target affords distinct imaging‐based monitoring of the cancer marker miR‐21 both in living cells and in vivo. At the same time, the architecture displays remarkable photothermal conversion efficiency (53.7%) and gives rise to outstanding therapy ability in vivo. This strategy offers new avenues for the intelligent quantification of miRNAs for simultaneous diagnoses and treatments of early‐stage cancers.