Glycosylated Star‐Shaped Conjugated Oligomers for Targeted Two‐Photon Fluorescence Imaging

Abstract A glucopyranose functionalized star‐shaped oligomer, N ‐tris{4,4′,4′′‐[(1 E )‐2‐(2‐{( E )‐2‐[4‐(benzo[ d ]thiazol‐2‐yl)phenyl]vinyl}‐9,9‐bis(6‐2‐amido‐2‐deoxy‐1‐thio‐β‐ D ‐glucopyranose‐hexyl)‐9 H ‐fluoren‐7‐yl)vinyl]phenyl}phenylamine (TVFVBN‐S‐NH 2 ), is synthesized for two‐photon fluorescence imaging. In water, TVFVBN‐S‐NH 2 self‐assembles into nanoparticles with an average diameter of ∼49 nm and shows a fluorescence quantum yield of 0.21. Two‐photon fluorescence measurements reveal that TVFVBN‐S‐NH 2 has a two‐photon absorption cross‐section of ∼1100 GM at 780 nm in water. The active amine group on the glucopyranose moiety allows further functionalization of TVFVBN‐S‐NH 2 with folic acid to yield TVFVBN‐S‐NH 2 FA with similar optical and physical properties as those for TVFVBN‐S‐NH 2 . Cellular imaging studies reveal that TVFVBN‐S‐NH 2 FA has increased uptake by MCF‐7 cells relative to that for TVFVBN‐S‐NH 2 , due to specific interactions between folic acid and folate receptors on the MCF‐7 cell membrane. This study demonstrates the effectiveness of glycosylation as a molecular engineering strategy to yield water‐soluble materials with a large two‐photon absorption (TPA) cross‐section for targeted cancer‐cell imaging.