Kumar, PhanindraPhanindraKumarMishra, TriptiTriptiMishraSanyam, NoneNoneSanyamMondal, AnirbanAnirbanMondalBasu, SudiptaSudiptaBasu2025-08-312025-08-312025-02-1710.1021/acsabm.4c017222-s2.0-85215605115https://d8.irins.org/handle/IITG2025/2825339835412Golgi 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.falseaggregation-induced-emission | density functional theory | endoplasmic reticulum | Golgi apparatus | internal charge transfer | molecular simulationsArticle257664221524-153217 February 20251arJournal3