Migration from Lysosome to Nucleus: Monitoring Lysosomal Alkalization-Related Biological Processes with an Aminofluorene-Based Probe

Abstract

Aberrant lysosomal alkalization is associated with various biological processes, such as oxidative stress, cell apoptosis, ferroptosis, etc. Herein, we developed a novel aminofluorene-based fluorescence probe named FAN to monitor the lysosomal alkalization-related biological processes by its migration from lysosome to nucleus. FAN possessed NIR emission, large Stokes shift, high pH stability, and high photostability, making it suitable for real-time and long-term bioimaging. As a lysosomotropic molecule, FAN can accumulate in lysosomes first and then migrate to the nucleus by right of its binding capability to DNA after lysosomal alkalization. In this manner, FAN was successfully used to monitor these physiological processes which triggered lysosomal alkalization in living cells, including oxidative stress, cell apoptosis, and ferroptosis. More importantly, at higher concentrations, FAN could also serve as a stable nucleus dye for the fluorescence imaging of the nucleus in living cells and tissues. This novel multifunctional fluorescence probe shows great promise for application in lysosomal alkalization-related visual research and nucleus imaging.

Recent Development of Lysosome-Targeted Organic Fluorescent Probes for Reactive Oxygen Species

“…Firstly, morpholine and other amine-based lysosome-targeting probes can potentially lead to toxicity due to their alkalinizing effect on lysosomal pH. For instance, the alkalinization of lysosomal pH can disrupt the proper functioning of lysosomes, impairing enzyme activity and hindering cellular waste degradation [ 78 , 79 ]. To mitigate the potential toxicities associated with these probes, researchers should meticulously optimize their experimental conditions, including probe concentrations and exposure times.…”

Conjugated Oligoelectrolyte with DNA Affinity for Enhanced Nuclear Imaging and Precise DNA Quantification

“…The fluorescence intensity of the emission spectra was directly proportional to DNA concentrations, showing a maximum blue shift (∆λ max = 37 nm) with increasing DNA concentration (Figure 2a). The binding constant, calculated using the Scatchard equation, was found to be 1.32 × 10 6 M −1 , with an R 2 value of approximately 0.9906, comparable to that of ethidium bromide (10 6 M −1 ) [35,36]. Notably, the fluorescence intensity at 439 nm with 10.6 mM DNA was 4.9 times higher than that of COE-S3 alone (inset of Figure 2b), while no significant fluorescence enhancement was observed with RNA (Figure S4).…”

A dual-labeling fluorescent probe to track lysosomal polarity and endoplasmic reticulum dynamics during ferroptosis

“…12 Currently, ferroptotic mechanisms in organelles have been widely reported, such as lysosomal alkalization and continuous generation of lipid droplets (LDs), but alterations in the lysosomal polarity and ER dynamics during ferroptosis remain poorly understood. 1,13 Therefore, establishing an approach that detects polarity and visualizes the ER and lysosomes for ferroptosis is a significant yet challenging task.…”