Construction of a TICT-AIE-Integrated Unimolecular Platform for Imaging Lipid Droplet–Mitochondrion Interactions in Live Cells and <i>In Vivo</i>

Abstract

Inter-organelle interactions play a vital role in diverse biological processes. Thus, chemical tools are highly desirable for understanding the spatiotemporal dynamic interplay among organelles in live cells and <i>in vivo</i>. However, designing such tools is still a great challenge due to the lack of universal design strategies. To break this bottleneck, herein, a novel unimolecular platform integrating the twisted intramolecular charge transfer (TICT) and aggregation-induced emission (AIE) dual mechanisms was proposed. As a proof of concept, two organelles, lipid droplets (LDs) and mitochondria, were selected as models. Also, the first TICT-AIE integration molecule, <b>BETA-1</b>, was designed for simultaneous and dual-color imaging of LDs and mitochondria. <b>BETA-1</b> can simultaneously target LDs and mitochondria due to its lipophilicity and cationic structure and emit cyan fluorescence in LDs and red fluorescence in mitochondria. Using <b>BETA-1</b>, for the first time, we obtained long-term tracking of dynamic LD-mitochondrion interactions and identified several impressive types of dynamic interactions between these two organelles. More importantly, the increase in LD-mitochondrion interactions during ferroptosis was revealed with <b>BETA-1</b>, suggesting that intervening in the LD-mitochondrion interactions may modulate this cell death. <b>BETA-1</b> was also successfully applied for <i>in vivo</i> imaging of LD-mitochondrion interactions in <i>C. elegans</i>. This study not only provides an effective tool for uncovering LD-mitochondrion interactions and deciphering related biological processes but also sheds light on the design of new probes with an integrated TICT-AIE mechanism for imaging of inter-organelle interactions.