Polystyrene‐Based Matrix to Enhance the Fluorescence of Aggregation‐Induced Emission Luminogen for Fluorescence‐Guided Surgery

Abstract Achieving ultrabright fluorogens is a key issue for fluorescence‐guided surgery (FGS). Fluorogens with aggregation‐induced emission (AIEgens) are potential agents for FGS on the benefit of the bright fluorescence in physiological conditions. Herein, the fluorescence brightness of AIEgen is further improved by preparing the nanoparticle using a polystyrene‐based matrix and utilizing it for tumor FGS with a high signal‐to‐background ratio. After encapsulating AIEgen into polystyrene‐poly (ethylene glycol) (PS‐PEG), the fluorescence intensity of the prepared AIE@PS‐PEG nanoparticles is multiple times that of nanoparticles in 1, 2‐distearoyl‐sn‐glycero‐3‐phosphoethanolamine‐poly (ethylene glycol) (DSPE‐PEG), a commonly used polymer matrix for nanoparticle preparation. Molecular dynamics simulations suggest that higher free energy is required for the outer rings of AIEgen to rotate in polystyrene than in the DSPE, indicating that the benzene rings in polystyrene can restrict the intramolecular motions of AIEgen better than the alkyl chain in DSPE‐PEG. Fluorescence correlation microscopy detections suggest that the triplet excited state of AIEgens is less in PS‐PEG than in DSPE‐PEG. The restricted intramolecular motions and suppressed triplet excited state result in ultrabright AIE@PS‐PEG nanoparticles, which are more conducive to illuminating tumor tissues in the intestine for FGS. The illumination of metastatic tumors in lungs by AIE@PS‐PEG nanoparticles is also tried.