Azoreductase-Responsive Nanoprobe for Hypoxia-Induced Mitophagy Imaging

Mitophagy, as a crucial metabolic process, plays an essential role in maintaining cellular and tissue homeostasis. Various stresses especially hypoxia could improve intracellular reactive oxygen species (ROS) level to induce mitophagy. However, high-specific fluorescence imaging of mitophagy in living cells under hypoxia is still a challenge. Based on this, we report an azoreductase-responsive nanoprobe (termed Micelle@Mito-rHP@TATp, MCM@TATp) by encapsulating cationic spiropyrane derivative (Mito-rHP) to realize specific imaging of mitophagy in living cells under hypoxia. An azoreductase-responsive amphiphilic polymer, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-azo-N-[maleimide(polyethylene glycol-2000) (Mal-PEG2000-Azo-DSPE), was first self-assembled into a micelle in aqueous solution. Meanwhile, the synthetic Mito-rHP encapsulated into this formed micelle to construct MCM. By modifying the surface of MCM with cell-penetrating peptide (TATp) to form MCM@TATp, the nanoprobe could avoid endolysosomal...