A Multi‐responsive Fluorescent Probe Reveals Mitochondrial Nucleoprotein Dynamics with Reactive Oxygen Species Regulation through Super‐resolution Imaging

Abstract

Understanding the biomolecular interactions in a specific organelle has been a long‐standing challenge because it requires super‐resolution imaging to resolve the spatial locations and dynamic interactions of multiple biomacromolecules. Two key difficulties are the scarcity of suitable probes for super‐resolution nanoscopy and the complications that arise from the use of multiple probes. Herein, we report a quinolinium derivative probe that is selectively enriched in mitochondria and switches on in three different fluorescence modes in response to hydrogen peroxide (H2O2), proteins, and nucleic acids, enabling the visualization of mitochondrial nucleoprotein dynamics. STED nanoscopy reveals that the proteins localize at mitochondrial cristae and largely fuse with nucleic acids to form nucleoproteins, whereas increasing H2O2 level leads to disassociation of nucleic acid–protein complexes.

Oxidative burst as a continuous H2O2 supplier for tumor oxygenation in photodynamic therapy

“…Endogenous H 2 O 2 in tumor cells was mainly produced in mitochondria. 36,37 ROS generation in the lysosome changed the lysosomal membrane permeabilization (LMP), which was verified by the acridine orange (AO) release experiment (Fig. 3B2).…”

Progress on the Physiological Function of Mitochondrial DNA and Its Specific Detection and Therapy

“…There is also a positively charged probe QVD‐B designed by Yang et al . to be internalized by mitochondria through the negatively charged mitochondrial membrane [60] . The borate in the structure of the probe can be removed through reacting with H 2 O 2 , converting quinolinium into a quinoline derivative (QVD).…”

Activation of apoptosis by rationally constructing NIR amphiphilic AIEgens: surmounting the shackle of mitochondrial membrane potential for amplified tumor ablation

“…12,23,28 Actually, the ROS produced by commonly used photosensitizers targeted to the mitochondria cause a decrease in the mitochondrial membrane potential. 12 This greatly weakens the targeting effect owing to the decrease of electrostatic interaction, a common phenomenon in mitochondrial fluorescent dyes research, [29][30][31] probably leading to photosensitizers' leakage and further limiting its ability to effectively kill cancer cells, which ultimately weakening the therapeutic effect. In addition, the decrease in fluorescence quantum yield and ROS production caused by the aggregation-caused quenching (ACQ) of most conventional photosensitizers with large π-planar hydrophobic structures is also a therapeutic hindrance.…”