Indomethacin-Naphthalimide-Based AIEgen for Illuminating Golgi Apparatus

Abstract

Golgi apparatus (GA) is a complex organelle controlling subcellular protein modifications, sorting, and transport. Dysregulation in GA leads to cancer development and metastasis. Consequently, development of small molecule fluorophores for illuminating GA in cancer cells remains a major challenge. To address this, herein, a small molecule library of four aggregation-induced emissive probes (AIEgens) is designed and synthesized, having (a) indomethacin, a nonsteroidal anti-inflammatory drug (NSAID) for GA homing; (b) 1,8-naphthalimide-N,N′-disubstituted aniline as AIE inducer; and (c) amide/ester linkage between NSAID and AIE inducer. All the library members exhibited excellent AIE property in THF/water binary solvent systems through self-assembly in water. Interestingly, one of the library members (compound 13), consisting of napthalimide-N,N′-dimethyl aniline as AIE inducer and amide linkage, efficiently homes into the GA of HCT-116 colon cancer cells within 30 min and self-assembled into 2D nanoscale materials, as shown by scanning electron and atomic force microscopy and confirmed by molecular dynamics (MD) simulations. Moreover, quantum mechanical calculations revealed intramolecular charge transfer (CT) between N,N′-dimethyl aniline (donor) and naphthalimide (acceptor) as the underlying mechanism of the photophysical properties of compound 13. This novel AIEgen can serve as a chemical biology tool to visualize GA in cancer cells for next-generation cancer therapeutics.