Dual‐Organelle‐Targeted Fluorescent Probe for Lipid Droplets and Endoplasmic Reticulum Using Bay‐Region Substituted Perylene Diimides

In the complex cellular microenvironment, lipid droplets (LDs) and the endoplasmic reticulum (ER) are essential for maintaining cellular homeostasis. Their interactions are crucial for regulating processes such as lipid metabolism. Nevertheless, simultaneously monitoring these two organelles remains a challenging task. In this study, a dual-organelle-targeted perylene diimides (PDIs) based probe, LD-ER-PDI, by incorporating a 2-azetidinone substituent in the bay-region and two distinct targeting groups for LDs and ER at opposite ends of the imide positions was developed, enabling discrimination between LDs and ER. Moreover, it can effectively visualize the dynamic behaviors of LDs and ER under starvation and oleic acid-treated conditions, and also allows real-time monitoring of LDs formation from the ER. This work not only provides a valuable tool for studying the dynamic interactions between LDs and ER but also highlights a strategy for designing dual-organelle-targeted fluorescent probes.