Rational Design of Organelle-Targeting/Migration Fluorescent Probes via Bidirectional Regulatory Strategies and Computational Simulations

The establishment of organelle-targeted and inwardly migratable fluorescent probes is important for studying apoptosis mechanisms and understanding the process. By fine-tuning the precise localization of the probes and their migration from the mitochondria to the nucleus, it is possible to image changes in organelle dynamics and the entire apoptotic process. However, existing probes lack a universal design strategy to image the dynamic behavior of organelles at all stages of apoptosis with high specificity, and methods still face significant challenges in resolving the molecular mechanisms of probe migration at the atomic scale. Here, a carbazole backbone platform (Car-X) for fluorescent probes was constructed by organelle-targeting methods and computational simulations. The relevant physical parameters verified the feasibility of the Car-X design. Through the bidirectional regulation strategy of "multivalency principle" and hydrophilic/hydrophobic design, Car-X achieves specific targeting to the cell membrane, mitochondria and nucleus, as well as the shift of mitochondria to nucleus migration when mitochondria are damaged. In addition, the visualization of Car-X on the three organelles facilitates the presentation of different stages of apoptosis in the simulation of intelligent biological processes. This strategy of bidirectional modulation of fluorescent probes by computationally assisted simulations provides new ideas for the design of organelle optical probes, which is expected to advance the research in organelle-related fields.