Triphenylamine-Naphthalimide-Based "On-Off-On" AIEgen for Imaging Golgi Apparatus and Endoplasmic Reticulum

Golgi apparatus (GA) and endoplasmic reticulum (ER) are two of the interesting subcellular organelles that are critical for protein synthesis, folding, processing, post-translational modifications, and secretion. Consequently, dysregulation in GA and ER and cross-talk between them are implicated in numerous diseases including cancer. As a result, simultaneous visualization of the GA and ER in cancer cells is extremely crucial for developing cancer therapeutics. To address this, herein, we have designed and synthesized a 1,8-napthalimide-based small molecule (AIE-GA-ER) consisting of phenylsulfonamide as Golgi-ER homing and triphenylamine-napthalimide as aggregation-induced emission (AIE) triggering moieties. AIE-GA-ER exhibited remarkable "on-off-on" AIE properties in THF/water binary solvent system due to aggregated "on-state" in pure THF and 80% water in THF. Molecular dynamic simulations and density functional theory (DFT) calculations exhibited the underlying mechanism of the emissive property of AIE-GA-ER to be the interplay between intramolecular charge transfer (ICT) stabilization and aggregation in THF, DMSO, and water. AIE-GA-ER efficiently homed into the GA and ER of HCT-116 colon cancer cells within 15-30 min as well as noncancerous human retinal epithelial pigment cells (RPE-1) within 3 h with minimum toxicity. This AIEgen has the potential to illuminate the Golgi apparatus and ER simultaneously in cancer cells to understand the chemical biology of their cross-talk for next-generation cancer therapeutics.