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

Self‐sustaining afterglow molecules (SAMs) offer high simplicity, reproducibility, and design flexibility compared to common multi‐component systems. To date, only a few SAMs have been reported. However, these studies mainly focus on probe selection and screening, without providing an guidance for constructing SAMs from the bottom up. Herein, we report the molecular design and tuning of boron dipyrromethene derivatives (BDs), with structural engineering to enhance the singlet oxygen (1O2) reactivity and photosensitivity, aiming to construct SAMs for activatable afterglow imaging. The optimized BDI‐NPs achieve afterglow luminescence at 780 nm following the precise structural creation of BDI, which serves as the role of afterglow initiator, substrate, and relay unit meantime. The BDI can be further customized into an activatable afterglow probe (BDIS‐NPs), capable of simultaneously activated fluorescence and afterglow signals for sensing hydrogen disulfide (H2S). 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 H2S 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.