Mitochondria MicroRNA Spatial Imaging via pH-Responsive Exonuclease-Assisted AIE Nanoreporter

Mitochondrial microRNAs (mitomiRs) critically orchestrate mitochondrial functions. Spatial imaging of mitomiRs is essential to understand its clinical value in diagnosis and prognosis. However, the direct monitoring of mitomiRs in living cells remains a key challenge. Herein, we report an AIE nanoreporter strategy for mitomiRs imaging in living cells through pH-controlled exonuclease (Exo)-assisted target cycle signal amplification. The AIE-labeled DNA detection probes are conjugated on Exo III encapsulated polymeric nanoparticles (NPs) via consecutive adenines (polyA). The amplified sensing functions are off during the cytoplasm delivery process, and it can be spatially switched from off to on when in the alkaline mitochondria (about pH 8) after triphenylphosphonium (TPP)-mediated mitochondrial targeting. Where the NPs degraded to release Exo III and cancer-specific mitomiRs hybridize with AIE-labeled DNA detection probes to expose the cleavage site of released Exo III, enabling spatially restricted mitomiRs imaging. The mitomiRs expression fluctuation was also realized. This study contributes to a facile strategy that could easily extend to a broad application for the understanding of mitomiRs-related pathological processes.