Molecular Engineering of a Self‐Sustaining Modular Afterglow Scaffold for In Vivo Activatable Imaging

Abstract Self‐sustaining afterglow molecules (SAMs) offer high simplicity, reproducibility, and design flexibility compared to common multicomponent systems. To date, only a few SAMs have been reported. However, these studies mainly focus on probe selection and screening, without providing the guidance for constructing SAMs from the bottom up. Herein, we report the molecular design and tuning of a boron dipyrromethene derivative (BDI), with structural engineering to enhance the singlet oxygen ( 1 O 2 ) reactivity and photosensitivity, aiming to construct SAMs for activatable afterglow imaging. The optimized BDI is customized into water‐soluble nanoparticles (i.e., BDI‐NPs) aided by an amphiphilic polymer, achieving all‐in‐one afterglow luminescence with a peak at 780 nm. An activatable afterglow probe (i.e., BDIS‐NPs) is fabricated, which can simultaneously activate fluorescence and afterglow signals in the presence of hydrogen disulfide (H 2 S). Owing to the elimination of autofluorescence and high activation contrast of the afterglow signal, BDIS‐NPs enables early monitoring of lipopolysaccharide (LPS)‐induced acute lung injury within 15 min and sensitive visualization of H 2 S accumulation in the brain of schizophrenia mice with a high signal‐to‐background ratio (SBR), which is not achievable by fluorescence imaging. This study provides an in‐depth understanding and design guidelines for SAMs and activatable afterglow imaging.